3-32106593-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000429432.5(GPD1L):c.-71+764C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 1,000,430 control chromosomes in the GnomAD database, including 798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (199 hom., cov: 33)
  • Exomes 𝑓: 0.035 (599 hom.)
• Consequence: GPD1L ENST00000429432.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.152

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 3-32106593-C-T is Benign according to our data. Variant chr3-32106593-C-T is described in ClinVar as [Benign]. Clinvar id is 1259211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPD1L	NM_015141.4			upstream_gene_variant		ENST00000282541.10
GPD1L	XM_006713068.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPD1L	ENST00000429432.5	c.-71+764C>T		intron_variant		4
GPD1L	ENST00000282541.10			upstream_gene_variant		1	NM_015141.4	P1
GPD1L	ENST00000425459.5			upstream_gene_variant		4
GPD1L	ENST00000428684.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7058 AN: 151952 Hom.: 199 Cov.: 33

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0221

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0337

Gnomad OTH AF: 0.0459

GnomAD4 exome AF: 0.0348 AC: 29519 AN: 848370 Hom.: 599 Cov.: 11 AF XY: 0.0353 AC XY: 14719 AN XY: 417370

Gnomad4 AFR exome AF: 0.0620

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.0265

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.0373

Gnomad4 NFE exome AF: 0.0317

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.0465 AC: 7066 AN: 152060 Hom.: 199 Cov.: 33 AF XY: 0.0477 AC XY: 3549 AN XY: 74364

Gnomad4 AFR AF: 0.0560

Gnomad4 AMR AF: 0.0835

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.0445

Gnomad4 FIN AF: 0.0421

Gnomad4 NFE AF: 0.0337

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0430 Hom.: 24

Bravo AF: 0.0502

Asia WGS AF: 0.0540 AC: 185 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Benign	0.93

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: rs1077601; hg19: chr3-32148085;