rs34278284

Positions:

chr3-32128109-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015141.4(GPD1L):c.81T>C(p.Asn27Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,613,394 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 4 hom. )

Consequence

GPD1L
NM_015141.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.82

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 3-32128109-T-C is Benign according to our data. Variant chr3-32128109-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 190760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-32128109-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.82 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00489 (745/152336) while in subpopulation AFR AF= 0.0166 (690/41572). AF 95% confidence interval is 0.0156. There are 9 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 745 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1L	NM_015141.4 link	c.81T>C	p.Asn27Asn	synonymous_variant	2/8	ENST00000282541.10	NP_055956.1	Q8N335
GPD1L	XM_006713068.3 link	c.81T>C	p.Asn27Asn	synonymous_variant	2/7		XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000282541.10 link	c.81T>C	p.Asn27Asn	synonymous_variant	2/8	1	NM_015141.4	ENSP00000282541.6		Q8N335

Frequencies

GnomAD3 genomes

AF:

0.00487

AC:

742

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00137

AC:

345

AN:

251096

Hom.:

AF XY:

0.00102

AC XY:

138

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000512

AC:

748

AN:

1461058

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

309

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.00489

AC:

745

AN:

152336

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

354

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0166

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.00602

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 28, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Brugada syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Brugada syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2015

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

-0.50

CADD

Benign

8.5

DANN

Benign

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over