VCV000038577.9 - ClinVar

NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser)

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.

(4)

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.

Uncertain significance

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.1177G>A (p.Gly393Ser)

Variation ID: 38577 Accession: VCV000038577.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3p25.1 3: 15645093 (GRCh38) [ NCBI UCSC ] 3: 15686600 (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 26, 2017	Feb 20, 2024	Dec 5, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370658.1:c.1177G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357587.1:p.Gly393Ser	missense
NM_000060.4:c.1237G>A	NP_000051.1:p.Gly413Ser	missense
NM_001281723.4:c.1177G>A	NP_001268652.2:p.Gly393Ser	missense
NM_001281724.3:c.1177G>A	NP_001268653.2:p.Gly393Ser	missense
NM_001281725.3:c.1177G>A	NP_001268654.1:p.Gly393Ser	missense
NM_001323582.2:c.1177G>A	NP_001310511.1:p.Gly393Ser	missense
NM_001370752.1:c.1015+162G>A		intron variant
NM_001370753.1:c.399+3036G>A		intron variant
NM_001407364.1:c.1177G>A	NP_001394293.1:p.Gly393Ser	missense
NM_001407365.1:c.1177G>A	NP_001394294.1:p.Gly393Ser	missense
NM_001407366.1:c.1177G>A	NP_001394295.1:p.Gly393Ser	missense
NM_001407367.1:c.1177G>A	NP_001394296.1:p.Gly393Ser	missense
NM_001407368.1:c.1177G>A	NP_001394297.1:p.Gly393Ser	missense
NM_001407369.1:c.1177G>A	NP_001394298.1:p.Gly393Ser	missense
NM_001407370.1:c.1177G>A	NP_001394299.1:p.Gly393Ser	missense
NM_001407371.1:c.1177G>A	NP_001394300.1:p.Gly393Ser	missense
NM_001407372.1:c.1177G>A	NP_001394301.1:p.Gly393Ser	missense
NM_001407373.1:c.1177G>A	NP_001394302.1:p.Gly393Ser	missense
NM_001407374.1:c.1177G>A	NP_001394303.1:p.Gly393Ser	missense
NM_001407375.1:c.1177G>A	NP_001394304.1:p.Gly393Ser	missense
NM_001407376.1:c.1177G>A	NP_001394305.1:p.Gly393Ser	missense
NM_001407377.1:c.1177G>A	NP_001394306.1:p.Gly393Ser	missense
NM_001407378.1:c.1177G>A	NP_001394307.1:p.Gly393Ser	missense
NC_000003.12:g.15645093G>A
NC_000003.11:g.15686600G>A
NG_008019.2:g.48742G>A
NG_008019.3:g.48743G>A

... more HGVS ... less HGVS

Protein change

G393S

Other names

G413S
p.Gly413Ser

Canonical SPDI

NC_000003.12:15645092: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.

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

Trans-Omics for Precision Medicine (TOPMed) 0.00002

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

dbSNP: rs374141881 ClinGen: CA278392 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	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Dec 5, 2023	RCV000032020.10
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 22, 2021	RCV003480039.1

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 (Dec 05, 2023)	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: SCV000630321.4 First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024	Publications: PubMed (1) PubMed: 25144890 Comment: This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 413 of the BTD protein (p.Gly413Ser). … (more) This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 413 of the BTD protein (p.Gly413Ser). This variant is present in population databases (rs374141881, gnomAD 0.003%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 25144890). ClinVar contains an entry for this variant (Variation ID: 38577). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Dec 14, 2017)	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000800639.1 First in ClinVar: May 30, 2018 Last updated: May 30, 2018	Publications: PubMed (1) PubMed: 25144890
Uncertain significance (Dec 22, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV004226053.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Comment: PP3, PM2 Number of individuals with the variant: 1
Uncertain significance (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001461223.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021

Comment:

This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 413 of the BTD protein (p.Gly413Ser). This variant is present in population databases (rs374141881, gnomAD 0.003%). This missense change has been observed in individual(s) with partial biotinidase deficiency (PMID: 25144890). ClinVar contains an entry for this variant (Variation ID: 38577). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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
Outcomes of individuals with profound and partial biotinidase deficiency ascertained by newborn screening in Michigan over 25 years.	Jay AM	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25144890

Text-mined citations for rs374141881 ...

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 08, 2024

ClinVar Genomic variation as it relates to human health

NM_001370658.1(BTD):c.1177G>A (p.Gly393Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs374141881 ...