Genetic Variant VMA21:p.Gly7Arg (chrX-151396858-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001363810.1(VMA21):c.19G>C(p.Gly7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 13688 hom., 17503 hem., cov: 21)

Exomes 𝑓: 0.50 ( 34664 hom. 75315 hem. )

Failed GnomAD Quality Control

Consequence

VMA21
NM_001363810.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.736

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:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4144747E-5).

BP6

Variant X-151396858-G-C is Benign according to our data. Variant chrX-151396858-G-C is described in ClinVar as [Benign]. Clinvar id is 1684210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1 link	c.19G>C	p.Gly7Arg	missense_variant	Exon 1 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
VMA21	ENST00000370361.5 link	c.19G>C	p.Gly7Arg	missense_variant	Exon 2 of 4	5	ENSP00000359386.1	Q3ZAQ7-2
ENSG00000287918	ENST00000660681.2 link	n.280C>G		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1 link	n.161C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

62315

AN:

109233

Hom.:

13679

Cov.:

AF XY:

0.552

AC XY:

17468

AN XY:

31621

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.496

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.547

Gnomad OTH

AF:

0.526

GnomAD3 exomes

AF:

0.461

AC:

46235

AN:

100226

Hom.:

7620

AF XY:

0.460

AC XY:

16402

AN XY:

35662

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.309

Gnomad ASJ exome

AF:

0.489

Gnomad EAS exome

AF:

0.173

Gnomad SAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.541

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.502

AC:

205927

AN:

409878

Hom.:

34664

Cov.:

AF XY:

0.500

AC XY:

75315

AN XY:

150492

show subpopulations

Gnomad4 AFR exome

AF:

0.762

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.544

Gnomad4 OTH exome

AF:

0.510

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.571

AC:

62355

AN:

109278

Hom.:

13688

Cov.:

AF XY:

0.553

AC XY:

17503

AN XY:

31676

show subpopulations

Gnomad4 AFR

AF:

0.753

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.496

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.547

Gnomad4 OTH

AF:

0.528

Alfa

AF:

0.432

Hom.:

3356

Bravo

AF:

0.561

TwinsUK

AF:

0.538

AC:

1994

ALSPAC

AF:

0.541

AC:

1564

ExAC

AF:

0.456

AC:

7873

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

X-linked myopathy with excessive autophagy

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.94

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.54

DANN

Benign

0.66

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.28

MetaRNN

Benign

0.000014

MetaSVM

Benign

-0.94

PROVEAN

Benign

0.18

REVEL

Benign

0.049

Sift

Pathogenic

0.0

Vest4

0.032

ClinPred

0.0059

GERP RS

-2.6

gMVP

0.053

Splicing

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