VCV000038593.18 - ClinVar

NM_001370658.1(BTD):c.1224C>T (p.Tyr408=)

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.

(9)

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/Likely 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_001370658.1(BTD):c.1224C>T (p.Tyr408=)

Variation ID: 38593 Accession: VCV000038593.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.1 3: 15645140 (GRCh38) [ NCBI UCSC ] 3: 15686647 (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	Mar 29, 2015	Sep 29, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370658.1:c.1224C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357587.1:p.Tyr408=	synonymous
NM_000060.4:c.1284C>T	NP_000051.1:p.Tyr428=	synonymous
NM_001281723.4:c.1224C>T	NP_001268652.2:p.Tyr408=	synonymous
NM_001281724.3:c.1224C>T	NP_001268653.2:p.Tyr408=	synonymous
NM_001281725.3:c.1224C>T	NP_001268654.1:p.Tyr408=	synonymous
NM_001281726.2:c.*3002C>T
NM_001323582.2:c.1224C>T	NP_001310511.1:p.Tyr408=	synonymous
NM_001370752.1:c.1015+209C>T		intron variant
NM_001370753.1:c.399+3083C>T		intron variant
NM_001407364.1:c.1224C>T	NP_001394293.1:p.Tyr408=	synonymous
NM_001407365.1:c.1224C>T	NP_001394294.1:p.Tyr408=	synonymous
NM_001407366.1:c.1224C>T	NP_001394295.1:p.Tyr408=	synonymous
NM_001407367.1:c.1224C>T	NP_001394296.1:p.Tyr408=	synonymous
NM_001407368.1:c.1224C>T	NP_001394297.1:p.Tyr408=	synonymous
NM_001407369.1:c.1224C>T	NP_001394298.1:p.Tyr408=	synonymous
NM_001407370.1:c.1224C>T	NP_001394299.1:p.Tyr408=	synonymous
NM_001407371.1:c.1224C>T	NP_001394300.1:p.Tyr408=	synonymous
NM_001407372.1:c.1224C>T	NP_001394301.1:p.Tyr408=	synonymous
NM_001407373.1:c.1224C>T	NP_001394302.1:p.Tyr408=	synonymous
NM_001407374.1:c.1224C>T	NP_001394303.1:p.Tyr408=	synonymous
NM_001407375.1:c.1224C>T	NP_001394304.1:p.Tyr408=	synonymous
NM_001407376.1:c.1224C>T	NP_001394305.1:p.Tyr408=	synonymous
NM_001407377.1:c.1224C>T	NP_001394306.1:p.Tyr408=	synonymous
NM_001407378.1:c.1224C>T	NP_001394307.1:p.Tyr408=	synonymous
NM_001407379.1:c.1015+209C>T		intron variant
NM_001407380.1:c.399+3083C>T		intron variant
NM_001407398.1:c.399+3083C>T		intron variant
NM_001407399.1:c.399+3083C>T		intron variant
NM_001407400.1:c.399+3083C>T		intron variant
NM_001407401.1:c.399+3083C>T		intron variant
NC_000003.12:g.15645140C>T
NC_000003.11:g.15686647C>T
NG_008019.3:g.48790C>T

... more HGVS ... less HGVS

Protein change

Other names

Y428Y

Canonical SPDI

NC_000003.12:15645139:C:T

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.

0.01098 (T)

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

Exome Aggregation Consortium (ExAC) 0.00378

1000 Genomes Project 0.01098

1000 Genomes Project 30x 0.01109

The Genome Aggregation Database (gnomAD) 0.01185

Trans-Omics for Precision Medicine (TOPMed) 0.01260

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01284

Links

ClinGen: CA145707 dbSNP: rs35145938 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.
BTD		-	-	GRCh38 GRCh37	670	756

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.
Biotinidase deficiency	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000032025.18
not specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Nov 16, 2021	RCV000078063.22
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Oct 23, 2019	RCV000429839.13

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: SCV000301784.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Oct 23, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001890270.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Comment: This variant is associated with the following publications: (PMID: 15776412, 26361991, 28498829, 25174816, 25967232, 20224900, 19757147)
Benign (Jul 30, 2021)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV002774190.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Publications: PubMed (3) PubMed: 15776412‚ 26361991‚ 25174816
Benign (Dec 30, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000511804.1 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017
Benign (Jun 19, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000109901.8 First in ClinVar: Jan 17, 2014 Last updated: Oct 02, 2016	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD Number of individuals with the variant: 3 Sex: mixed
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000630322.4 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024
Likely benign (Sep 17, 2014)	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015)) Method: literature only	Biotinidase deficiency (Autosomal recessive inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000220687.2 First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022	Publications: PubMed (4) PubMed: 19757147‚ 20224900‚ 15776412‚ 25174816
Likely Benign (Nov 16, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004847527.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Comment: The p.Tyr428Tyr variant in BTD is classified as likely benign because it does not alter an amino acid residue, is not located within the splice … (more) The p.Tyr428Tyr variant in BTD is classified as likely benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. It has been identified in 3.8% (942/24956) of African chromosomes, including 15 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1, BP4, BP7. (less)
Likely 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: SCV005264664.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Comment:

The p.Tyr428Tyr variant in BTD is classified as likely benign because it does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact on splicing. It has been identified in 3.8% (942/24956) of African chromosomes, including 15 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BS1, BP4, BP7.

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
Biotinidase deficiency: Spectrum of molecular, enzymatic and clinical information from newborn screening Ontario, Canada (2007-2014).	Gannavarapu S	Molecular genetics and metabolism	2015	PMID: 26361991
Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients.	Borsatto T	BMC medical genetics	2014	PMID: 25174816
Profound biotinidase deficiency: a rare disease among native Swedes.	Ohlsson A	Journal of inherited metabolic disease	2010	PMID: 20224900
High incidence of profound biotinidase deficiency detected in newborn screening blood spots in the Somalian population in Minnesota.	Sarafoglou K	Journal of inherited metabolic disease	2009	PMID: 19757147
Biotinidase deficiency: novel mutations and their biochemical and clinical correlates.	Wolf B	Human mutation	2005	PMID: 15776412
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BTD	-	-	-	-

Text-mined citations for rs35145938 ...

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 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001370658.1(BTD):c.1224C>T (p.Tyr408=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs35145938 ...