VCV000007582.26 - ClinVar

NM_006214.4(PHYH):c.85C>T (p.Pro29Ser)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(14)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006214.4(PHYH):c.85C>T (p.Pro29Ser)

Variation ID: 7582 Accession: VCV000007582.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10p13 10: 13298236 (GRCh38) [ NCBI UCSC ] 10: 13340236 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 6, 2014	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_006214.4:c.85C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006205.1:p.Pro29Ser	missense
NM_001037537.2:c.-167+1184C>T		intron variant
NM_001323080.2:c.-216C>T		5 prime UTR
NM_001323082.2:c.85C>T	NP_001310011.1:p.Pro29Ser	missense
NM_001323083.2:c.85C>T	NP_001310012.1:p.Pro29Ser	missense
NM_001323084.2:c.-167+1184C>T		intron variant
NC_000010.11:g.13298236G>A
NC_000010.10:g.13340236G>A
NG_012862.1:g.6895C>T
	O14832:p.Pro29Ser

... more HGVS ... less HGVS

Protein change

P29S

Other names

PHYH, PRO29SER (rs28938169)
NM_006214.3(PHYH):c.85C>T(p.Pro29Ser)

Canonical SPDI

NC_000010.11:13298235:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.09764 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.09764

1000 Genomes Project 30x 0.09806

Trans-Omics for Precision Medicine (TOPMed) 0.13727

The Genome Aggregation Database (gnomAD), exomes 0.14756

The Genome Aggregation Database (gnomAD) 0.15001

Exome Aggregation Consortium (ExAC) 0.15038

Links

ClinGen: CA154245 UniProtKB: O14832#VAR_017482 OMIM: 602026.0006 dbSNP: rs28938169 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PHYH		-	-	GRCh38 GRCh37	450	513

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Benign (5)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000008020.18
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	May 9, 2014	RCV000117911.18
Phytanic acid storage disease	Benign (5)	criteria provided, multiple submitters, no conflicts	Sep 5, 2021	RCV000306854.12

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000311434.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (May 09, 2014)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000227384.5 First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PHYH Number of individuals with the variant: 1 Sex: mixed
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Phytanic acid storage disease Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138001.1 First in ClinVar: Jan 10, 2020 Last updated: Jan 10, 2020
Benign (Sep 26, 2018)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001899317.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Comment: This variant is associated with the following publications: (PMID: 10767344, 25525159, 20220177, 20981092, 11555634)
Benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Phytanic acid storage disease Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002029637.1 First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001732225.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Phytanic acid storage disease Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803605.1 First in ClinVar: May 30, 2018 Last updated: May 30, 2018	Comment: This variant is interpreted as a Benign - Stand Alone, for Refsum disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => … (more) This variant is interpreted as a Benign - Stand Alone, for Refsum disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. (less)
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Phytanic acid storage disease Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000361494.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005323902.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000152187.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. (less)
Benign (May 01, 2000)	no assertion criteria provided Method: literature only	RECLASSIFIED - PHYTANOYL-CoA HYDROXYLASE POLYMORPHISM Affected status: not provided Allele origin: germline	OMIM Accession: SCV000028225.4 First in ClinVar: Apr 04, 2013 Last updated: Feb 05, 2017	Publications: PubMed (1) PubMed: 10767344 Exome Variant Server NHLBI GO Exome (more...) Exome Variant Server NHLBI GO Exome Sequencing Project (ESP), Seattle, WA. http://evs.gs.washington.edu/EVS 2012. Comment on evidence: This variant, formerly titled REFSUM DISEASE, ADULT, 1, has been reclassified as a polymorphism. As of December 2012, the pro29-to-ser (P29S) variant had an overall … (more) This variant, formerly titled REFSUM DISEASE, ADULT, 1, has been reclassified as a polymorphism. As of December 2012, the pro29-to-ser (P29S) variant had an overall population frequency of 20% (Exome Variant Server, 2012). In addition, the patients reported by Jansen et al. (2000) with this mutation had additional mutations in the PHYH gene that may have been causative and the P29S mutant was found to be fully active. In 2 patients (patients 1 and 2) with Refsum disease (266500), Jansen et al. (2000) found an 85C-T transition in the PHYH gene, leading to a P29S substitution. The patients also had a truncating mutation (602026.0002) and either 589G-C or 648C-T leading to missense mutations E197Q or H220Y, respectively. Patient 2 also had 526C-A transversion leading to a Q176K (602026.0007) substitution. (less)
Benign (-)	no assertion criteria provided Method: clinical testing	Phytanic acid storage disease Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000732935.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Oct 26, 2015)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801745.1 First in ClinVar: Feb 05, 2017 Last updated: Feb 05, 2017
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001920328.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
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Comment:

This variant is interpreted as a Benign - Stand Alone, for Refsum disease, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Human phytanoyl-CoA hydroxylase: resolution of the gene structure and the molecular basis of Refsum's disease.	Jansen GA	Human molecular genetics	2000	PMID: 10767344
Exome Variant Server NHLBI GO Exome Sequencing Project (ESP), Seattle, WA. http://evs.gs.washington.edu/EVS 2012.	-	-	-	-
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PHYH	-	-	-	-

Text-mined citations for rs28938169 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_006214.4(PHYH):c.85C>T (p.Pro29Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs28938169 ...