3-32106485-T-G

Variant names:

• chr3-32106485-T-G
• rs6805518
• ENST00000429432.5:c.-71+656T>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000429432.5(GPD1L):​c.-71+656T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 367,448 control chromosomes in the GnomAD database, including 143,619 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56171 hom., cov: 35)
  • Exomes 𝑓: 0.90 (87448 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.39

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-32106485-T-G is Benign according to our data. Variant chr3-32106485-T-G is described in ClinVar as [Benign]. Clinvar id is 671016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPD1L	NM_015141.4	c.-227T>G		upstream_gene_variant		ENST00000282541.10	NP_055956.1
GPD1L	XM_006713068.3	c.-227T>G		upstream_gene_variant			XP_006713131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPD1L	ENST00000282541.10	c.-227T>G		upstream_gene_variant		1	NM_015141.4	ENSP00000282541.6

Frequencies

GnomAD3 genomes AF: 0.865 AC: 129978 AN: 150264 Hom.: 56145 Cov.: 35

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.872

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.897 AC: 194804 AN: 217080 Hom.: 87448 Cov.: 3 AF XY: 0.898 AC XY: 99686 AN XY: 111020

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.928

Gnomad4 ASJ exome AF: 0.903

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.913

Gnomad4 FIN exome AF: 0.903

Gnomad4 NFE exome AF: 0.905

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.865 AC: 130051 AN: 150368 Hom.: 56171 Cov.: 35 AF XY: 0.869 AC XY: 63892 AN XY: 73540

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.874

Alfa AF: 0.869 Hom.: 2903

Bravo AF: 0.850

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6805518; hg19: chr3-32147977;