3-32140269-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015141.4(GPD1L):c.408C>T(p.Asp136Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,640 control chromosomes in the GnomAD database, including 17,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2795 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14351 hom. )

Consequence

GPD1L
NM_015141.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.37

Publications

15 publications found

Variant links:

Genes affected

GPD1L (HGNC:28956): (glycerol-3-phosphate dehydrogenase 1 like) The protein encoded by this gene catalyzes the conversion of sn-glycerol 3-phosphate to glycerone phosphate. The encoded protein is found in the cytoplasm, associated with the plasma membrane, where it binds the sodium channel, voltage-gated, type V, alpha subunit (SCN5A). Defects in this gene are a cause of Brugada syndrome type 2 (BRS2) as well as sudden infant death syndrome (SIDS). [provided by RefSeq, Jul 2010]

GPD1L Gene-Disease associations (from GenCC):

Brugada syndrome 2
Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

GPD1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 3-32140269-C-T is Benign according to our data. Variant chr3-32140269-C-T is described in ClinVar as Benign. ClinVar VariationId is 260571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPD1L	NM_015141.4 link	c.408C>T	p.Asp136Asp	synonymous_variant	Exon 4 of 8	ENST00000282541.10	NP_055956.1	Q8N335
GPD1L	XM_006713068.3 link	c.267C>T	p.Asp89Asp	synonymous_variant	Exon 3 of 7		XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000282541.10 link	c.408C>T	p.Asp136Asp	synonymous_variant	Exon 4 of 8	1	NM_015141.4	ENSP00000282541.6		Q8N335

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25981

AN:

151994

Hom.:

2792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0957

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.162

GnomAD2 exomes

AF:

0.123

AC:

30986

AN:

251324

AF XY:

0.123

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.0710

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.000761

Gnomad FIN exome

AF:

0.0970

Gnomad NFE exome

AF:

0.135

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.133

AC:

194805

AN:

1461528

Hom.:

14351

Cov.:

AF XY:

0.133

AC XY:

96939

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.307

AC:

10290

AN:

33468

American (AMR)

AF:

0.0795

AC:

3554

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3170

AN:

26132

East Asian (EAS)

AF:

0.000630

AC:

AN:

39700

South Asian (SAS)

AF:

0.138

AC:

11861

AN:

86246

European-Finnish (FIN)

AF:

0.0955

AC:

5102

AN:

53416

Middle Eastern (MID)

AF:

0.138

AC:

796

AN:

5768

European-Non Finnish (NFE)

AF:

0.137

AC:

151915

AN:

1111692

Other (OTH)

AF:

0.134

AC:

8092

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

9134

18267

27401

36534

45668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5528

11056

16584

22112

27640

<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:

0.171

AC:

25996

AN:

152112

Hom.:

2795

Cov.:

AF XY:

0.167

AC XY:

12430

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.299

AC:

12394

AN:

41454

American (AMR)

AF:

0.118

AC:

1802

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

415

AN:

3470

East Asian (EAS)

AF:

0.00251

AC:

AN:

5174

South Asian (SAS)

AF:

0.141

AC:

678

AN:

4812

European-Finnish (FIN)

AF:

0.0957

AC:

1014

AN:

10600

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9154

AN:

68018

Other (OTH)

AF:

0.159

AC:

335

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1027

2055

3082

4110

5137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.148

Hom.:

5793

Bravo

AF:

0.177

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

EpiCase

AF:

0.136

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Brugada syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jun 19, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.61

PhyloP100

1.4

Mutation Taster

=15/85

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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