NM_001370658.1:c.1353T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001370658.1(BTD):c.1353T>C(p.Cys451Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 1,614,080 control chromosomes in the GnomAD database, including 9,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.096 ( 967 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8961 hom. )

Consequence

BTD
NM_001370658.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.203

Publications

15 publications found

Variant links:

Genes affected

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

BTD Gene-Disease associations (from GenCC):

biotinidase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

BTD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 3-15645269-T-C is Benign according to our data. Variant chr3-15645269-T-C is described in ClinVar as Benign. ClinVar VariationId is 25088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.203 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTD	NM_001370658.1 link	c.1353T>C	p.Cys451Cys	synonymous_variant	Exon 4 of 4	ENST00000643237.3	NP_001357587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTD	ENST00000643237.3 link	c.1353T>C	p.Cys451Cys	synonymous_variant	Exon 4 of 4		NM_001370658.1	ENSP00000495254.2		P43251-4

Frequencies

GnomAD3 genomes

AF:

0.0959

AC:

14585

AN:

152080

Hom.:

958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0709

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0822

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0860

Gnomad OTH

AF:

0.0965

GnomAD2 exomes

AF:

0.126

AC:

31678

AN:

251426

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.0833

Gnomad NFE exome

AF:

0.0885

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0987

AC:

144351

AN:

1461882

Hom.:

8961

Cov.:

AF XY:

0.0995

AC XY:

72394

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0653

AC:

2186

AN:

33480

American (AMR)

AF:

0.169

AC:

7562

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0475

AC:

1241

AN:

26134

East Asian (EAS)

AF:

0.331

AC:

13135

AN:

39700

South Asian (SAS)

AF:

0.143

AC:

12370

AN:

86258

European-Finnish (FIN)

AF:

0.0876

AC:

4677

AN:

53420

Middle Eastern (MID)

AF:

0.0548

AC:

316

AN:

5768

European-Non Finnish (NFE)

AF:

0.0867

AC:

96440

AN:

1112004

Other (OTH)

AF:

0.106

AC:

6424

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

8636

17272

25909

34545

43181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3778

7556

11334

15112

18890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0959

AC:

14600

AN:

152198

Hom.:

967

Cov.:

AF XY:

0.0981

AC XY:

7304

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0707

AC:

2935

AN:

41536

American (AMR)

AF:

0.114

AC:

1742

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

194

AN:

3468

East Asian (EAS)

AF:

0.371

AC:

1919

AN:

5174

South Asian (SAS)

AF:

0.170

AC:

815

AN:

4808

European-Finnish (FIN)

AF:

0.0822

AC:

872

AN:

10606

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0860

AC:

5850

AN:

67990

Other (OTH)

AF:

0.103

AC:

219

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

635

1270

1905

2540

3175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0901

Hom.:

1533

Bravo

AF:

0.0987

Asia WGS

AF:

0.276

AC:

956

AN:

3478

EpiCase

AF:

0.0782

EpiControl

AF:

0.0860

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Biotinidase deficiency

Benign:4

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Aug 31, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2021

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.3

(source)

DANN

Benign

0.54

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over