Variant rs376724853 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015141.4(GPD1L):c.837C>G(p.Phe279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPD1L
NM_015141.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.442

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:

GPD1L (HGNC:):

GPD1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD1L	NM_015141.4 linkuse as main transcript	c.837C>G	p.Phe279Leu	missense_variant	6/8	ENST00000282541.10	NP_055956.1	Q8N335
GPD1L	XM_006713068.3 linkuse as main transcript	c.696C>G	p.Phe232Leu	missense_variant	5/7		XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000282541.10 linkuse as main transcript	c.837C>G	p.Phe279Leu	missense_variant	6/8	1	NM_015141.4	ENSP00000282541.6		Q8N335

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248336

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

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

Cardiovascular phenotype

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 24, 2021

The p.F279L variant (also known as c.837C>G), located in coding exon 6 of the GPD1L gene, results from a C to G substitution at nucleotide position 837. The phenylalanine at codon 279 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.64

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.51

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.51

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.36

Sift

Benign

0.046

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.65

MutPred

0.60

Gain of disorder (P = 0.093);

MVP

0.63

MPC

1.3

ClinPred

0.82

GERP RS

-3.7

Varity_R

0.82

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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