NM_001370658.1(BTD):c.383G>A (p.Arg128His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003226165.1

Allele description [Variation Report for NM_001370658.1(BTD):c.383G>A (p.Arg128His)]

NM_001370658.1(BTD):c.383G>A (p.Arg128His)

Gene:

BTD:biotinidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p25.1

Genomic location:

Preferred name:

NM_001370658.1(BTD):c.383G>A (p.Arg128His)

HGVS:

NC_000003.12:g.15642041G>A
NG_008019.2:g.45690G>A
NM_000060.4:c.443G>A
NM_001281723.4:c.383G>A
NM_001281724.3:c.383G>A
NM_001281725.3:c.383G>A
NM_001281726.3:c.383G>A
NM_001323582.2:c.383G>A
NM_001370658.1:c.383G>AMANE SELECT
NM_001370752.1:c.383G>A
NM_001370753.1:c.383G>A
NM_001407364.1:c.383G>A
NM_001407365.1:c.383G>A
NM_001407366.1:c.383G>A
NM_001407367.1:c.383G>A
NM_001407368.1:c.383G>A
NM_001407369.1:c.383G>A
NM_001407370.1:c.383G>A
NM_001407371.1:c.383G>A
NM_001407372.1:c.383G>A
NM_001407373.1:c.383G>A
NM_001407374.1:c.383G>A
NM_001407375.1:c.383G>A
NM_001407376.1:c.383G>A
NM_001407377.1:c.383G>A
NM_001407378.1:c.383G>A
NM_001407379.1:c.383G>A
NM_001407380.1:c.383G>A
NM_001407381.1:c.446G>A
NM_001407382.1:c.383G>A
NM_001407383.1:c.383G>A
NM_001407384.1:c.383G>A
NM_001407386.1:c.383G>A
NM_001407388.1:c.383G>A
NM_001407390.1:c.383G>A
NM_001407392.1:c.383G>A
NM_001407394.1:c.383G>A
NM_001407395.1:c.383G>A
NM_001407396.1:c.383G>A
NM_001407397.1:c.383G>A
NM_001407398.1:c.383G>A
NM_001407399.1:c.383G>A
NM_001407400.1:c.383G>A
NM_001407401.1:c.383G>A
NP_000051.1:p.Arg148His
NP_001268652.2:p.Arg128His
NP_001268652.2:p.Arg128His
NP_001268653.2:p.Arg128His
NP_001268654.1:p.Arg128His
NP_001268654.1:p.Arg128His
NP_001268655.2:p.Arg128His
NP_001268655.2:p.Arg128His
NP_001310511.1:p.Arg128His
NP_001310511.1:p.Arg128His
NP_001357587.1:p.Arg128His
NP_001357681.1:p.Arg128His
NP_001357682.1:p.Arg128His
NP_001394293.1:p.Arg128His
NP_001394294.1:p.Arg128His
NP_001394295.1:p.Arg128His
NP_001394296.1:p.Arg128His
NP_001394297.1:p.Arg128His
NP_001394298.1:p.Arg128His
NP_001394299.1:p.Arg128His
NP_001394300.1:p.Arg128His
NP_001394301.1:p.Arg128His
NP_001394302.1:p.Arg128His
NP_001394303.1:p.Arg128His
NP_001394304.1:p.Arg128His
NP_001394305.1:p.Arg128His
NP_001394306.1:p.Arg128His
NP_001394307.1:p.Arg128His
NP_001394308.1:p.Arg128His
NP_001394309.1:p.Arg128His
NP_001394310.1:p.Arg149His
NP_001394311.1:p.Arg128His
NP_001394312.1:p.Arg128His
NP_001394313.1:p.Arg128His
NP_001394315.1:p.Arg128His
NP_001394317.1:p.Arg128His
NP_001394319.1:p.Arg128His
NP_001394321.1:p.Arg128His
NP_001394323.1:p.Arg128His
NP_001394324.1:p.Arg128His
NP_001394325.1:p.Arg128His
NP_001394326.1:p.Arg128His
NP_001394327.1:p.Arg128His
NP_001394328.1:p.Arg128His
NP_001394329.1:p.Arg128His
NP_001394330.1:p.Arg128His
NC_000003.11:g.15683548G>A
NM_001281723.3:c.383G>A
NM_001281725.2:c.383G>A
NM_001281726.2:c.383G>A
NM_001323582.1:c.383G>A
NM_001370658.1:c.383G>A

Protein change:

R128H

Links:

dbSNP: rs367902696

NCBI 1000 Genomes Browser:

rs367902696

Molecular consequence:

NM_000060.4:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281723.4:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281724.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281725.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001281726.3:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001323582.2:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370658.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370752.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001370753.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407364.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407365.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407366.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407367.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407368.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407369.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407370.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407371.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407372.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407373.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407374.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407375.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407376.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407377.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407378.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407379.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407380.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407381.1:c.446G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407382.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407383.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407384.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407386.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407388.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407390.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407392.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407394.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407395.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407396.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407397.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407398.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407399.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407400.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407401.1:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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ATP synthase CF1 beta subunit, partial (chloroplast) [Erodium guttatum]
ATP synthase CF1 beta subunit, partial (chloroplast) [Erodium guttatum]
gi|557477971|gb|AHA11157.1|

Protein
LOC105369161 [Homo sapiens]
LOC105369161 [Homo sapiens]
Gene ID:105369161

Gene
ASH2LP4 ASH2L pseudogene 4 [Homo sapiens]
ASH2LP4 ASH2L pseudogene 4 [Homo sapiens]
Gene ID:100736412

Gene
MRPS16P3 mitochondrial ribosomal protein S16 pseudogene 3 [Homo sapiens]
MRPS16P3 mitochondrial ribosomal protein S16 pseudogene 3 [Homo sapiens]
Gene ID:338388

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922837	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20224900, 33312878 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922837

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 22, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Profound biotinidase deficiency: a rare disease among native Swedes.

Ohlsson A, Guthenberg C, Holme E, von Döbeln U.

J Inherit Metab Dis. 2010 Dec;33 Suppl 3:S175-80. doi: 10.1007/s10545-010-9065-y. Epub 2010 Mar 12.

PubMed [citation]

PMID:: 20224900

High frequency of biotinidase deficiency in Italian population identified by newborn screening.

Funghini S, Tonin R, Malvagia S, Caciotti A, Donati MA, Morrone A, la Marca G.

Mol Genet Metab Rep. 2020 Dec;25:100689. doi: 10.1016/j.ymgmr.2020.100689.

PubMed [citation]

PMID:: 33312878
PMCID:: PMC7719957

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003922837.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: BTD c.383G>A (p.Arg128His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251272 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in BTD causing biotinidase deficiency (6e-05 vs 0.0046), allowing no conclusion about variant significance. c.383G>A has been reported in the literature in the compound heterozygous state in an individual affected with partial biotinidase deficiency and in the mother of a proband with partial biotinidase deficiency, who was asymptomatic but was found to have decreased plasma biotinidase activity outside the normal range (Ohlsson_2010, Funghini_2020). These data do not allow any strong conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as either likely pathogenic (n=3) or VUS (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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