Variant 16-69316091-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_013245.3(VPS4A):c.105G>A(p.Ala35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,613,396 control chromosomes in the GnomAD database, including 239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 128 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 111 hom. )

Consequence

VPS4A
NM_013245.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.94

Variant links:

Genes affected

VPS4A (HGNC:13488): (vacuolar protein sorting 4 homolog A) The protein encoded by this gene is a member of the AAA protein family (ATPases associated with diverse cellular activities), and is the homolog of the yeast Vps4 protein. In humans, two paralogs of the yeast protein have been identified. The former share a high degree of aa sequence similarity with each other, and also with yeast Vps4 and mouse Skd1 proteins. The mouse Skd1 (suppressor of K+ transport defect 1) has been shown to be really an yeast Vps4 ortholog. Functional studies indicate that both human paralogs associate with the endosomal compartments, and are involved in intracellular protein trafficking, similar to Vps4 protein in yeast. The gene encoding this paralog has been mapped to chromosome 16; the gene for the other resides on chromosome 18. [provided by RefSeq, Jul 2008]

VPS4A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 16-69316091-G-A is Benign according to our data. Variant chr16-69316091-G-A is described in ClinVar as [Benign]. Clinvar id is 784625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS4A	NM_013245.3 linkuse as main transcript	c.105G>A	p.Ala35=	synonymous_variant	2/11	ENST00000254950.13	NP_037377.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS4A	ENST00000254950.13 linkuse as main transcript	c.105G>A	p.Ala35=	synonymous_variant	2/11	1	NM_013245.3	ENSP00000254950	P1

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3346

AN:

152074

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00858

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00578

AC:

1439

AN:

248956

Hom.:

AF XY:

0.00432

AC XY:

583

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.0787

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000399

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00248

AC:

3627

AN:

1461204

Hom.:

111

Cov.:

AF XY:

0.00220

AC XY:

1598

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0796

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.0000756

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.00542

GnomAD4 genome

AF:

0.0220

AC:

3347

AN:

152192

Hom.:

128

Cov.:

AF XY:

0.0215

AC XY:

1599

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.00851

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.8

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over