NM_001363810.1:c.194G>T

Variant names:

• chrX-151397033-G-T
• rs753376606
• NM_001363810.1:c.194G>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>T​(p.Gly65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 389,199 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: 0.000023 (0 hom. 3 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=0.07777944).
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.194G>T	p.Gly65Val	missense_variant	Exon 1 of 3		NP_001350739.1
VMA21	NM_001017980.4	c.-276G>T		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.-276G>T		upstream_gene_variant		1	NM_001017980.4	ENSP00000333255.6

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD3 exomes AF: 0.0000237 AC: 2 AN: 84537 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 26317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000153

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000322

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000231 AC: 9 AN: 389199 Hom.: 0 Cov.: 0 AF XY: 0.0000219 AC XY: 3 AN XY: 136977

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000340

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000446

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	-0.75	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.2
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.0010
Sift	Uncertain	0.011	D
Sift4G	Benign	0.19	T
Vest4		0.073
MutPred		0.26		Gain of sheet (P = 0.0016);
MVP		0.35
ClinPred		0.022	T
GERP RS		-0.93
gMVP		0.49

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;