NM_001363810.1:c.19G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363810.1(VMA21):​c.19G>T​(p.Gly7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 21)
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08636907).

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>T	p.Gly7Cys	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>T	p.Gly7Cys	missense	Exon 2 of 4	ENSP00000359386.1	Q3ZAQ7-2
	ENSG00000287918	ENST00000660681.3		n.280C>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000287918	ENST00000664935.1		n.161C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 3356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.94
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.74
PROVEAN	Benign	0.37	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Vest4		0.089
MutPred		0.096		Loss of phosphorylation at S4 (P = 0.1161)
MVP		0.18
ClinPred		0.58	D
GERP RS		-2.6
PromoterAI		-0.029	Neutral
gMVP		0.087
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;