3-32159662-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015141.4(GPD1L):c.947G>C(p.Gly316Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GPD1L
NM_015141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.183

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19106382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPD1L	NM_015141.4 linkuse as main transcript	c.947G>C	p.Gly316Ala	missense_variant	7/8	ENST00000282541.10
GPD1L	XM_006713068.3 linkuse as main transcript	c.806G>C	p.Gly269Ala	missense_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GPD1L	ENST00000282541.10 linkuse as main transcript	c.947G>C	p.Gly316Ala	missense_variant	7/8	1	NM_015141.4	P1
GPD1L	ENST00000474846.5 linkuse as main transcript	n.871G>C		non_coding_transcript_exon_variant	2/3	2
GPD1L	ENST00000496151.1 linkuse as main transcript	n.448G>C		non_coding_transcript_exon_variant	2/3	2
GPD1L	ENST00000428684.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250908

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445228

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brugada syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Aug 28, 2021

This sequence change replaces glycine with alanine at codon 316 of the GPD1L protein (p.Gly316Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GPD1L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.35

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Pathogenic

0.80

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.28

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.060

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.18

Sift

Uncertain

0.026

Sift4G

Uncertain

0.040

Polyphen

0.024

Vest4

0.15

MutPred

0.54

Loss of catalytic residue at Q314 (P = 0.1199);

MVP

0.75

MPC

0.43

ClinPred

0.15

GERP RS

3.7

Varity_R

0.43

gMVP

0.44

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