9-125305140-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001282680.3(GAPVD1):c.1107G>A(p.Lys369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,605,182 control chromosomes in the GnomAD database, including 963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (499 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (464 hom.)
• Consequence: GAPVD1 NM_001282680.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.01

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 9-125305140-G-A is Benign according to our data. Variant chr9-125305140-G-A is described in ClinVar as [Benign]. Clinvar id is 1270828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPVD1	NM_001282680.3	c.1107G>A	p.Lys369=	synonymous_variant	6/28	ENST00000297933.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPVD1	ENST00000297933.11	c.1107G>A	p.Lys369=	synonymous_variant	6/28	1	NM_001282680.3	P3

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7148 AN: 152124 Hom.: 499 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00539

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00442

Gnomad OTH AF: 0.0425

GnomAD3 exomes AF: 0.0151 AC: 3792 AN: 251204 Hom.: 203 AF XY: 0.0124 AC XY: 1680 AN XY: 135782

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.00944

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00438

Gnomad FIN exome AF: 0.000554

Gnomad NFE exome AF: 0.00400

Gnomad OTH exome AF: 0.0150

GnomAD4 exome AF: 0.00828 AC: 12026 AN: 1452940 Hom.: 464 Cov.: 27 AF XY: 0.00772 AC XY: 5585 AN XY: 723500

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0147

Gnomad4 ASJ exome AF: 0.00948

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00455

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.00380

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0470 AC: 7162 AN: 152242 Hom.: 499 Cov.: 33 AF XY: 0.0455 AC XY: 3386 AN XY: 74440

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0206

Gnomad4 ASJ AF: 0.00980

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00441

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0230 Hom.: 116

Bravo AF: 0.0541

Asia WGS AF: 0.0160 AC: 56 AN: 3478

EpiCase AF: 0.00578

EpiControl AF: 0.00599

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 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	7.0
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs62637640; hg19: chr9-128067419;