rs141926826

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/20 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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

X-linked myopathy with excessive autophagy
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

VMA21 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
VMA21	NM_001017980.4 link	c.182A>G	p.Asn61Ser	missense_variant	Exon 3 of 3	ENST00000330374.7	NP_001017980.1
VMA21	NM_001363810.1 link	c.347A>G	p.Asn116Ser	missense_variant	Exon 3 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
VMA21	ENST00000330374.7 link	c.182A>G	p.Asn61Ser	missense_variant	Exon 3 of 3	1	NM_001017980.4	ENSP00000333255.6
VMA21	ENST00000370361.5 link	c.347A>G	p.Asn116Ser	missense_variant	Exon 4 of 4	5		ENSP00000359386.1
VMA21	ENST00000477649.1 link	n.262A>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

208

AN:

110477

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000535

AC:

AN:

183159

AF XY:

0.000370

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 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

African (AFR)

AF:

0.00557

AC:

147

AN:

26396

American (AMR)

AF:

0.000483

AC:

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19382

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40417

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.0000451

AC:

AN:

842011

Other (OTH)

AF:

0.000694

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00188

AC:

208

AN:

110529

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

AN XY:

32737

show subpopulations

African (AFR)

AF:

0.00613

AC:

186

AN:

30339

American (AMR)

AF:

0.00192

AC:

AN:

10393

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2635

East Asian (EAS)

AF:

0.00

AC:

AN:

3510

South Asian (SAS)

AF:

0.00

AC:

AN:

2539

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5865

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52850

Other (OTH)

AF:

0.000667

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000677

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

Dec 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Jan 09, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

2.8

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

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over