rs200045526

chr3-32159621-G-Achr3-32159621-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015141.4(GPD1L):c.906G>A(p.Pro302=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,612,708 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P302P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000092 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (2 hom.)
• Consequence: GPD1L NM_015141.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.70

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-32159621-G-A is Benign according to our data. Variant chr3-32159621-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 519277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.7 with no splicing effect.
• BS2: High AC in GnomAd at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPD1L	NM_015141.4	c.906G>A	p.Pro302=	synonymous_variant	7/8	ENST00000282541.10
GPD1L	XM_006713068.3	c.765G>A	p.Pro255=	synonymous_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPD1L	ENST00000282541.10	c.906G>A	p.Pro302=	synonymous_variant	7/8	1	NM_015141.4	P1
GPD1L	ENST00000474846.5	n.830G>A		non_coding_transcript_exon_variant	2/3	2
GPD1L	ENST00000496151.1	n.407G>A		non_coding_transcript_exon_variant	2/3	2
GPD1L	ENST00000428684.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000112 AC: 28 AN: 250890 Hom.: 0 AF XY: 0.000125 AC XY: 17 AN XY: 135774

Gnomad AFR exome AF: 0.000309

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.0000706

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000733 AC: 107 AN: 1460562 Hom.: 2 Cov.: 30 AF XY: 0.0000826 AC XY: 60 AN XY: 726650

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000583

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152146 Hom.: 1 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74310

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.000106

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 30, 2020

- -

Brugada syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 15, 2023

- -

Cardiovascular phenotype Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2016

This alteration is classified as likely 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	-0.80
Cadd	Benign	6.2
Dann	Benign	0.43

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

Other links and lift over

dbSNP: rs200045526; hg19: chr3-32201113;