Genetic Variant VMA21:p.Arg3Leu (chrX-151397316-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017980.4(VMA21):c.8G>T(p.Arg3Leu) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. R3R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

VMA21
NM_001017980.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

Publications

0 publications found

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]

VMA21 Gene-Disease associations (from GenCC):

X-linked myopathy with excessive autophagy
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

VMA21 links:

ENSG00000287918 (HGNC:):

ENSG00000287918 links:

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ACMG classification

Classification was made for transcript

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=0.17792583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017980.4. 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_001017980.4	MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 1 of 3	NP_001017980.1	Q3ZAQ7-1
	VMA21	NM_001363810.1		c.218+259G>T		intron	N/A	NP_001350739.1	Q3ZAQ7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VMA21	ENST00000330374.7	TSL:1 MANE Select	c.8G>T	p.Arg3Leu	missense	Exon 1 of 3	ENSP00000333255.6	Q3ZAQ7-1
VMA21	ENST00000932111.1		c.8G>T	p.Arg3Leu	missense	Exon 1 of 3	ENSP00000602170.1
VMA21	ENST00000370361.5	TSL:5	c.218+259G>T		intron	N/A	ENSP00000359386.1	Q3ZAQ7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1047468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

342012

African (AFR)

AF:

0.00

AC:

AN:

24882

American (AMR)

AF:

0.00

AC:

AN:

27905

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18630

East Asian (EAS)

AF:

0.00

AC:

AN:

27118

South Asian (SAS)

AF:

0.00

AC:

AN:

49772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3933

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

819103

Other (OTH)

AF:

0.00

AC:

AN:

44265

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.079

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0088

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.66

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.90

PhyloP100

3.4

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.076

Sift4G

Benign

0.13

Polyphen

0.65

Vest4

0.41

MutPred

0.22

Gain of methylation at K6 (P = 0.0935)

MVP

0.54

MPC

0.96

ClinPred

0.46

GERP RS

5.2

PromoterAI

0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over