Variant rs141926826 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001017980.4(VMA21):c.182A>G(p.Asn61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000368 in 1,208,466 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. N61N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 48 hem., cov: 22)

Exomes 𝑓: 0.00022 ( 0 hom. 54 hem. )

Consequence

VMA21
NM_001017980.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

VMA21 (HGNC:22082): (vacuolar ATPase assembly factor VMA21) This gene encodes a chaperone for assembly of lysosomal vacuolar ATPase.[provided by RefSeq, Jul 2012]

VMA21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008299381).

BP6

Variant X-151404934-A-G is Benign according to our data. Variant chrX-151404934-A-G is described in ClinVar as [Benign]. Clinvar id is 464819.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 48 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VMA21	NM_001017980.4 linkuse as main transcript	c.182A>G	p.Asn61Ser	missense_variant	3/3	ENST00000330374.7
VMA21	NM_001363810.1 linkuse as main transcript	c.347A>G	p.Asn116Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VMA21	ENST00000330374.7 linkuse as main transcript	c.182A>G	p.Asn61Ser	missense_variant	3/3	1	NM_001017980.4	P1	Q3ZAQ7-1
VMA21	ENST00000370361.5 linkuse as main transcript	c.347A>G	p.Asn116Ser	missense_variant	4/4	5			Q3ZAQ7-2
VMA21	ENST00000477649.1 linkuse as main transcript	n.262A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

208

AN:

110477

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

AN XY:

32675

show subpopulations

Gnomad AFR

AF:

0.00614

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00193

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.000675

GnomAD3 exomes

AF:

0.000535

AC:

AN:

183159

Hom.:

AF XY:

0.000370

AC XY:

AN XY:

67599

show subpopulations

Gnomad AFR exome

AF:

0.00654

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000526

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000216

AC:

237

AN:

1097937

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

363311

show subpopulations

Gnomad4 AFR exome

AF:

0.00557

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000451

Gnomad4 OTH exome

AF:

0.000694

GnomAD4 genome

AF:

0.00188

AC:

208

AN:

110529

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

AN XY:

32737

show subpopulations

Gnomad4 AFR

AF:

0.00613

Gnomad4 AMR

AF:

0.00192

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.000667

Alfa

AF:

0.000220

Hom.:

Bravo

AF:

0.00250

ESP6500AA

AF:

0.00678

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000560

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

VMA21-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

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). -

X-linked myopathy with excessive autophagy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 13, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0011

.;T

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.47

.;N

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.17

Sift

Benign

0.20

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.0

.;B

Vest4

0.029

MVP

0.43

MPC

0.62

ClinPred

0.0073

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.57

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