rs176451

Variant names:

• chrX-151396858-G-A
• rs176451
• NM_001363810.1:c.19G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-151396858-G-A
• chrX-151396858-G-C
• chrX-151396858-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736
• Publications: 5 publications found

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)

ENSG00000287918 (HGNC:):

ACMG classification

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

Sel.	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: 1 AN: 109286 Hom.: 0 Cov.: 21

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: 1 AN: 100226 AF XY: 0.00

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: 1 AN: 410034 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 150540

African (AFR) AF: 0.00 AC: 0 AN: 12382

American (AMR) AF: 0.00 AC: 0 AN: 26767

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14596

East Asian (EAS) AF: 0.00 AC: 0 AN: 24057

South Asian (SAS) AF: 0.0000265 AC: 1 AN: 37753

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2974

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 232507

Other (OTH) AF: 0.00 AC: 0 AN: 23084

GnomAD4 genome AF: 0.00000915 AC: 1 AN: 109286 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 31632

African (AFR) AF: 0.00 AC: 0 AN: 29918

American (AMR) AF: 0.00 AC: 0 AN: 10491

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2627

East Asian (EAS) AF: 0.000291 AC: 1 AN: 3436

South Asian (SAS) AF: 0.00 AC: 0 AN: 2448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52390

Other (OTH) AF: 0.00 AC: 0 AN: 1474

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	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.66
DANN	Benign	0.96
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.74
PROVEAN	Benign	0.24	N
REVEL	Benign	0.082
Sift	Pathogenic	0.0	D
Vest4		0.018
MutPred		0.082		Gain of phosphorylation at G7 (P = 0.0054)
MVP		0.30
ClinPred		0.24	T
GERP RS		-2.6
PromoterAI		-0.072	Neutral
gMVP		0.093
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs176451; hg19: chrX-150565330;