rs891766489

Variant names:

• chrX-151397011-G-A
• NM_001363810.1:c.172G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-151397011-G-A
• chrX-151397011-G-C
• chrX-151397011-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001363810.1(VMA21):​c.172G>A​(p.Glu58Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 403,606 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/12 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: not found (cov: 21)
  • Exomes 𝑓: 0.0000074 (0 hom. 2 hem.)
• Consequence: VMA21 NM_001363810.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10766405).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.172G>A	p.Glu58Lys	missense_variant	Exon 1 of 3		NP_001350739.1
VMA21	NM_001017980.4	c.-298G>A		upstream_gene_variant		ENST00000330374.7	NP_001017980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000330374.7	c.-298G>A		upstream_gene_variant		1	NM_001017980.4	ENSP00000333255.6

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000743 AC: 3 AN: 403606 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 2 AN XY: 147160

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: 0.0000266

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000864

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.89	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.035
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.057	T
Vest4		0.18
MutPred		0.28		Gain of MoRF binding (P = 0.0084);
MVP		0.53
ClinPred		0.23	T
GERP RS		3.7
gMVP		0.54

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-150565483;