VCV000381876.39 - ClinVar

NM_005050.4(ABCD4):c.1411C>T (p.Arg471Trp)

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.

(7)

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.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005050.4(ABCD4):c.1411C>T (p.Arg471Trp)

Variation ID: 381876 Accession: VCV000381876.39

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q24.3 14: 74290035 (GRCh38) [ NCBI UCSC ] 14: 74756738 (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	Dec 19, 2017	Oct 20, 2024	Jan 30, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_005050.4:c.1411C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005041.1:p.Arg471Trp	missense
NM_001353591.2:c.1285C>T	NP_001340520.1:p.Arg429Trp	missense
NM_001353592.2:c.1285C>T	NP_001340521.1:p.Arg429Trp	missense
NM_001353593.2:c.1150C>T	NP_001340522.1:p.Arg384Trp	missense
NM_001353594.2:c.1099C>T	NP_001340523.1:p.Arg367Trp	missense
NM_001353595.2:c.997C>T	NP_001340524.1:p.Arg333Trp	missense
NM_001353596.2:c.997C>T	NP_001340525.1:p.Arg333Trp	missense
NM_001353597.2:c.946C>T	NP_001340526.1:p.Arg316Trp	missense
NM_001353598.2:c.934C>T	NP_001340527.1:p.Arg312Trp	missense
NM_001353599.2:c.934C>T	NP_001340528.1:p.Arg312Trp	missense
NM_001353600.2:c.934C>T	NP_001340529.1:p.Arg312Trp	missense
NM_001353601.2:c.934C>T	NP_001340530.1:p.Arg312Trp	missense
NM_001353602.2:c.622C>T	NP_001340531.1:p.Arg208Trp	missense
NM_001353603.2:c.622C>T	NP_001340532.1:p.Arg208Trp	missense
NM_001353604.2:c.622C>T	NP_001340533.1:p.Arg208Trp	missense
NM_001353605.2:c.622C>T	NP_001340534.1:p.Arg208Trp	missense
NM_001353606.2:c.622C>T	NP_001340535.1:p.Arg208Trp	missense
NM_001353607.2:c.622C>T	NP_001340536.1:p.Arg208Trp	missense
NM_001353608.2:c.622C>T	NP_001340537.1:p.Arg208Trp	missense
NM_001353609.2:c.622C>T	NP_001340538.1:p.Arg208Trp	missense
NM_001353610.2:c.622C>T	NP_001340539.1:p.Arg208Trp	missense
NM_020324.3:c.934C>T	NP_064720.1:p.Arg312Trp	missense
NM_020325.3:c.1411C>T	NP_064730.1:p.Arg471Trp	missense
NR_003256.3:n.1305C>T		non-coding transcript variant
NC_000014.9:g.74290035G>A
NC_000014.8:g.74756738G>A
NG_032875.1:g.18030C>T

... more HGVS ... less HGVS

Protein change

R471W, R367W, R208W, R312W, R316W, R333W, R384W, R429W

Other names

p.Arg471Trp

Canonical SPDI

NC_000014.9:74290034: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.

0.00140 (A)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00115

1000 Genomes Project 0.00140

The Genome Aggregation Database (gnomAD), exomes 0.00155

The Genome Aggregation Database (gnomAD) 0.00163

Exome Aggregation Consortium (ExAC) 0.00168

Trans-Omics for Precision Medicine (TOPMed) 0.00171

1000 Genomes Project 30x 0.00172

Links

ClinGen: CA7266821 dbSNP: rs45568335 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.
ABCD4		-	-	GRCh38 GRCh37	430	452

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	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Aug 1, 2023	RCV000443723.31
Methylmalonic acidemia with homocystinuria, type cblJ	Conflicting interpretations of pathogenicity (3)	criteria provided, conflicting classifications	Jan 30, 2024	RCV000763942.14
ABCD4-related disorder	Likely benign (1)	no assertion criteria provided	Jul 9, 2024	RCV004758013.1

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.
Uncertain significance (Oct 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Methylmalonic acidemia with homocystinuria, type cblJ Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV000894888.1 First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019	Publications: PubMed (1) PubMed: 25741868 pmc: 4544753 pmc: 4544753 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Methylmalonic acidemia with homocystinuria, type cblJ Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001139484.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Likely benign (Oct 29, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000521558.4 First in ClinVar: Mar 08, 2017 Last updated: Apr 17, 2019	Comment: Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on … (more) Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20849526) (less)
Uncertain significance (Jan 06, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004227328.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Comment: BS1, PP3 Number of individuals with the variant: 2
Likely benign (Jan 30, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Methylmalonic acidemia with homocystinuria, type cblJ Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001113750.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Likely benign (Aug 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV001371596.24 First in ClinVar: Jul 16, 2020 Last updated: Oct 20, 2024	Comment: ABCD4: PP3, BS2 Number of individuals with the variant: 2
Likely benign (Jul 09, 2024)	no assertion criteria provided Method: clinical testing	ABCD4-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005344407.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20849526)

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs45568335 ...

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 Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_005050.4(ABCD4):c.1411C>T (p.Arg471Trp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs45568335 ...