Variant X-151396927-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000668689.1(ENSG00000287918):n.216G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000383 in 522,144 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.0000024 ( 0 hom. 0 hem. )

Consequence

ENST00000668689.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.237

Variant links:

Genes affected

(HGNC:):

links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13051894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VMA21	NM_001363810.1 linkuse as main transcript	c.88C>T	p.Arg30Cys	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000668689.1 linkuse as main transcript	n.216G>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110570

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32834

show subpopulations

Gnomad AFR

AF:

0.0000329

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000243

AC:

AN:

411574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

151736

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000428

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110570

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32834

show subpopulations

Gnomad4 AFR

AF:

0.0000329

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Mar 29, 2024

Variant summary: VMA21 c.-382C>T is located in the untranscribed region upstream of the VMA21 gene region. The variant was absent in 20650 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-382C>T in individuals affected with X-Linked Myopathy With Excessive Autophagy and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.4

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.40

M_CAP

Benign

0.0093

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

0.070

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.21

MutPred

0.29

Loss of solvent accessibility (P = 3e-04);

MVP

0.093

ClinPred

0.96

GERP RS

1.4

gMVP

0.13

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over