9-125301963-CTT-C

Position:

• chr9-125301963-CTT-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001282680.3(GAPVD1):​c.186-4_186-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 1,283,592 control chromosomes in the GnomAD database, including 24 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.013 (24 hom., cov: 30)
  • Exomes 𝑓: 0.061 (0 hom.)
• Consequence: GAPVD1 NM_001282680.3 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.192

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]

GAPVD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 9-125301963-CTT-C is Benign according to our data. Variant chr9-125301963-CTT-C is described in ClinVar as [Benign]. Clinvar id is 3055624.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPVD1	NM_001282680.3	c.186-4_186-3delTT		splice_region_variant, intron_variant		ENST00000297933.11	NP_001269609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPVD1	ENST00000297933.11	c.186-4_186-3delTT		splice_region_variant, intron_variant		1	NM_001282680.3	ENSP00000297933.6

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1682 AN: 130894 Hom.: 24 Cov.: 30

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00538

Gnomad ASJ AF: 0.000962

Gnomad EAS AF: 0.000219

Gnomad SAS AF: 0.000238

Gnomad FIN AF: 0.00334

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.000399

Gnomad OTH AF: 0.00625

GnomAD3 exomes AF: 0.0793 AC: 6478 AN: 81726 Hom.: 1 AF XY: 0.0788 AC XY: 3494 AN XY: 44362

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.0958

Gnomad ASJ exome AF: 0.0916

Gnomad EAS exome AF: 0.0819

Gnomad SAS exome AF: 0.0863

Gnomad FIN exome AF: 0.0390

Gnomad NFE exome AF: 0.0697

Gnomad OTH exome AF: 0.0793

GnomAD4 exome AF: 0.0605 AC: 69781 AN: 1152718 Hom.: 0 AF XY: 0.0605 AC XY: 34360 AN XY: 568354

Gnomad4 AFR exome AF: 0.0986

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.0548

Gnomad4 EAS exome AF: 0.0422

Gnomad4 SAS exome AF: 0.0672

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.0607

Gnomad4 OTH exome AF: 0.0607

GnomAD4 genome AF: 0.0129 AC: 1686 AN: 130874 Hom.: 24 Cov.: 30 AF XY: 0.0124 AC XY: 780 AN XY: 62800

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.00537

Gnomad4 ASJ AF: 0.000962

Gnomad4 EAS AF: 0.000220

Gnomad4 SAS AF: 0.000239

Gnomad4 FIN AF: 0.00334

Gnomad4 NFE AF: 0.000400

Gnomad4 OTH AF: 0.00621

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GAPVD1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 09, 2020

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

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: rs397893733; hg19: chr9-128064242;