rs753376606

Variant names:

• chrX-151397033-G-A
• rs753376606
• NM_001363810.1:c.194G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-151397033-G-A
• chrX-151397033-G-C
• chrX-151397033-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.194G>A​(p.Gly65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 500,328 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes 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 0.000027 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.000026 (0 hom. 6 hem.)
• Consequence: VMA21 NM_001363810.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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=0.07931459).
• BS2: High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.194G>A	p.Gly65Glu	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.194G>A	p.Gly65Glu	missense_variant	Exon 2 of 4	5		ENSP00000359386.1
ENSG00000287918	ENST00000660681.2	n.105C>T		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000668689.1	n.110C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0000270 AC: 3 AN: 111128 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33466

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000380

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000257 AC: 10 AN: 389200 Hom.: 0 Cov.: 0 AF XY: 0.0000438 AC XY: 6 AN XY: 136978

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: 0.0000274

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000401

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000270 AC: 3 AN: 111128 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 33466

Gnomad4 AFR AF: 0.0000327

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000380

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.9
DANN	Benign	0.87
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.042
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.24	T
Vest4		0.041
MutPred		0.16		Loss of loop (P = 0.0112);
MVP		0.38
ClinPred		0.15	T
GERP RS		-0.93
gMVP		0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs753376606; hg19: chrX-150565505;