Genetic Variant NM_001363810.1:c.19G>A (chrX-151396858-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363810.1(VMA21):c.19G>A(p.Gly7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000385 in 519,320 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000024 ( 0 hom. 0 hem. )

Consequence

VMA21
NM_001363810.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.736

Publications

5 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: Orphanet, Labcorp Genetics (formerly Invitae)

VMA21 links:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0654169).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363810.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VMA21	NM_001363810.1		c.19G>A	p.Gly7Ser	missense	Exon 1 of 3	NP_001350739.1	Q3ZAQ7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VMA21	ENST00000370361.5	TSL:5	c.19G>A	p.Gly7Ser	missense	Exon 2 of 4	ENSP00000359386.1	Q3ZAQ7-2
ENSG00000287918	ENST00000660681.3		n.280C>T		non_coding_transcript_exon	Exon 1 of 2
ENSG00000287918	ENST00000664935.1		n.161C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000915

AC:

AN:

109286

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000291

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000998

AC:

AN:

100226

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000244

AC:

AN:

410034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

150540

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12382

American (AMR)

AF:

0.00

AC:

AN:

26767

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14596

East Asian (EAS)

AF:

0.00

AC:

AN:

24057

South Asian (SAS)

AF:

0.0000265

AC:

AN:

37753

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2974

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

232507

Other (OTH)

AF:

0.00

AC:

AN:

23084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00000915

AC:

AN:

109286

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31632

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29918

American (AMR)

AF:

0.00

AC:

AN:

10491

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2627

East Asian (EAS)

AF:

0.000291

AC:

AN:

3436

South Asian (SAS)

AF:

0.00

AC:

AN:

2448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52390

Other (OTH)

AF:

0.00

AC:

AN:

1474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

3356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.66

(source)

DANN

Benign

0.96

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.29

M_CAP

Benign

0.0014

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.1

PhyloP100

-0.74

PROVEAN

Benign

0.24

REVEL

Benign

0.082

Sift

Pathogenic

0.0

Vest4

0.018

MutPred

0.082

Gain of phosphorylation at G7 (P = 0.0054)

MVP

0.30

ClinPred

0.24

GERP RS

-2.6

PromoterAI

-0.072

Neutral

(source)

gMVP

0.093

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over