X-151397011-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1PM2BP6

The NM_001363810.1(VMA21):​c.172G>T​(p.Glu58*) variant causes a stop gained 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. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 21)

Consequence

VMA21
NM_001363810.1 stop_gained

Scores

1
4

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.20
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant X-151397011-G-T is Benign according to our data. Variant chrX-151397011-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048775.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VMA21NM_001363810.1 linkc.172G>T p.Glu58* stop_gained Exon 1 of 3 NP_001350739.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VMA21ENST00000370361.5 linkc.172G>T p.Glu58* stop_gained Exon 2 of 4 5 ENSP00000359386.1 Q3ZAQ7-2
ENSG00000287918ENST00000660681.2 linkn.127C>A non_coding_transcript_exon_variant Exon 1 of 2
ENSG00000287918ENST00000664935.1 linkn.8C>A non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
21

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

VMA21-related disorder Benign:1
Nov 25, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
8.8
DANN
Uncertain
0.99
FATHMM_MKL
Benign
0.45
N
Vest4
0.13
GERP RS
3.7

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; API