9-125312528-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001282680.3(GAPVD1):c.1518T>C(p.Ile506=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.955 in 1,610,904 control chromosomes in the GnomAD database, including 734,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (71306 hom., cov: 31)
  • Exomes 𝑓: 0.95 (662921 hom.)
• Consequence: GAPVD1 NM_001282680.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

Genes affected

GAPVD1 (HGNC:23375): (GTPase activating protein and VPS9 domains 1) Enables GTPase activating protein binding activity and guanyl-nucleotide exchange factor activity. Involved in regulation of protein transport. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-125312528-T-C is Benign according to our data. Variant chr9-125312528-T-C is described in ClinVar as [Benign]. Clinvar id is 3060575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.039 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPVD1	NM_001282680.3	c.1518T>C	p.Ile506=	synonymous_variant	9/28	ENST00000297933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPVD1	ENST00000297933.11	c.1518T>C	p.Ile506=	synonymous_variant	9/28	1	NM_001282680.3	P3

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147182 AN: 152158 Hom.: 71244 Cov.: 31

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.978

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.969

GnomAD3 exomes AF: 0.967 AC: 240664 AN: 248854 Hom.: 116418 AF XY: 0.967 AC XY: 130199 AN XY: 134578

Gnomad AFR exome AF: 0.991

Gnomad AMR exome AF: 0.979

Gnomad ASJ exome AF: 0.977

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.993

Gnomad FIN exome AF: 0.975

Gnomad NFE exome AF: 0.946

Gnomad OTH exome AF: 0.964

GnomAD4 exome AF: 0.953 AC: 1390432 AN: 1458628 Hom.: 662921 Cov.: 33 AF XY: 0.955 AC XY: 692736 AN XY: 725652

Gnomad4 AFR exome AF: 0.993

Gnomad4 AMR exome AF: 0.978

Gnomad4 ASJ exome AF: 0.977

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.992

Gnomad4 FIN exome AF: 0.971

Gnomad4 NFE exome AF: 0.944

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.967 AC: 147303 AN: 152276 Hom.: 71306 Cov.: 31 AF XY: 0.969 AC XY: 72160 AN XY: 74452

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.962

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.978

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.970

Alfa AF: 0.954 Hom.: 111859

Bravo AF: 0.967

Asia WGS AF: 0.997 AC: 3466 AN: 3478

EpiCase AF: 0.953

EpiControl AF: 0.953

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FAM157B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.3
Dann	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs432757; hg19: chr9-128074807;