Variant chr16-69316132-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_013245.3(VPS4A):c.133+13A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,612,764 control chromosomes in the GnomAD database, including 52,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 6410 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46018 hom. )

Consequence

VPS4A
NM_013245.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.99

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 16-69316132-A-C is Benign according to our data. Variant chr16-69316132-A-C is described in ClinVar as [Benign]. Clinvar id is 1246081.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS4A	NM_013245.3 linkuse as main transcript	c.133+13A>C		intron_variant		ENST00000254950.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS4A	ENST00000254950.13 linkuse as main transcript	c.133+13A>C		intron_variant		1	NM_013245.3	P1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41998

AN:

151894

Hom.:

6389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.0488

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.273

GnomAD3 exomes

AF:

0.212

AC:

52587

AN:

247992

Hom.:

6473

AF XY:

0.210

AC XY:

28240

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.0509

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.220

GnomAD4 exome

AF:

0.245

AC:

357913

AN:

1460752

Hom.:

46018

Cov.:

AF XY:

0.242

AC XY:

176000

AN XY:

726630

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.206

Gnomad4 EAS exome

AF:

0.0622

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.277

AC:

42054

AN:

152012

Hom.:

6410

Cov.:

AF XY:

0.271

AC XY:

20153

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.210

Gnomad4 EAS

AF:

0.0489

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.259

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.236

Hom.:

3625

Bravo

AF:

0.280

Asia WGS

AF:

0.126

AC:

437

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

DANN

Benign

0.29

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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