9-125302394-T-G

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.597T>G(p.Thr199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00857 in 1,614,062 control chromosomes in the GnomAD database, including 686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (102 hom., cov: 31)
  • Exomes 𝑓: 0.0081 (584 hom.)
• Consequence: GAPVD1 NM_001282680.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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=-0.52).
• BP6: Variant 9-125302394-T-G is Benign according to our data. Variant chr9-125302394-T-G is described in ClinVar as [Benign]. Clinvar id is 1283313.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPVD1	NM_001282680.3	c.597T>G	p.Thr199=	synonymous_variant	5/28	ENST00000297933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPVD1	ENST00000297933.11	c.597T>G	p.Thr199=	synonymous_variant	5/28	1	NM_001282680.3	P3

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1963 AN: 152148 Hom.: 101 Cov.: 31

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0801

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.0264 AC: 6620 AN: 251186 Hom.: 354 AF XY: 0.0228 AC XY: 3096 AN XY: 135794

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.0839

Gnomad SAS exome AF: 0.0251

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.0190

GnomAD4 exome AF: 0.00812 AC: 11875 AN: 1461796 Hom.: 584 Cov.: 33 AF XY: 0.00820 AC XY: 5963 AN XY: 727202

Gnomad4 AFR exome AF: 0.00155

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.000536

Gnomad4 EAS exome AF: 0.0950

Gnomad4 SAS exome AF: 0.0245

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000175

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.0129 AC: 1963 AN: 152266 Hom.: 102 Cov.: 31 AF XY: 0.0145 AC XY: 1082 AN XY: 74452

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0878

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0113

Alfa AF: 0.00477 Hom.: 59

Bravo AF: 0.0189

Asia WGS AF: 0.0530 AC: 184 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000119

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

May 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.2
Dann	Benign	0.83

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

Other links and lift over

dbSNP: rs10986694; hg19: chr9-128064673; COSMIC: COSV52927812; COSMIC: COSV52927812;