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. Variant got -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. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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]

ENSG00000287918 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0654169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.19G>A	p.Gly7Ser	missense_variant	Exon 1 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000370361.5	c.19G>A	p.Gly7Ser	missense_variant	Exon 2 of 4	5		ENSP00000359386.1
ENSG00000287918	ENST00000660681.2	n.280C>T		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1	n.161C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000915 AC: 1 AN: 109286 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 31632

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

GnomAD3 exomes AF: 0.00000998 AC: 1 AN: 100226 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 35662

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 SAS exome AF: 0.0000727

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000265

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000291

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
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
gMVP		0.093

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs176451; hg19: chrX-150565330;