X-151396890-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001363810.1(VMA21):ā€‹c.51G>Cā€‹(p.Glu17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00089 in 522,449 control chromosomes in the GnomAD database, including 4 homozygotes. There are 119 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0026 ( 3 hom., 79 hem., cov: 21)
Exomes š‘“: 0.00043 ( 1 hom. 40 hem. )

Consequence

VMA21
NM_001363810.1 missense

Scores

1
10

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0860
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0035504699).
BP6
Variant X-151396890-G-C is Benign according to our data. Variant chrX-151396890-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1690444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VMA21NM_001363810.1 linkc.51G>C p.Glu17Asp missense_variant Exon 1 of 3 NP_001350739.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VMA21ENST00000370361.5 linkc.51G>C p.Glu17Asp missense_variant Exon 2 of 4 5 ENSP00000359386.1 Q3ZAQ7-2
ENSG00000287918ENST00000660681.2 linkn.248C>G non_coding_transcript_exon_variant Exon 1 of 2
ENSG00000287918ENST00000664935.1 linkn.129C>G non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
AF:
0.00256
AC:
283
AN:
110576
Hom.:
3
Cov.:
21
AF XY:
0.00238
AC XY:
78
AN XY:
32804
show subpopulations
Gnomad AFR
AF:
0.00873
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00132
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:
0.0000379
Gnomad OTH
AF:
0.00135
GnomAD3 exomes
AF:
0.000507
AC:
52
AN:
102574
Hom.:
1
AF XY:
0.000348
AC XY:
13
AN XY:
37366
show subpopulations
Gnomad AFR exome
AF:
0.00842
Gnomad AMR exome
AF:
0.000471
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000435
AC:
179
AN:
411828
Hom.:
1
Cov.:
0
AF XY:
0.000263
AC XY:
40
AN XY:
151894
show subpopulations
Gnomad4 AFR exome
AF:
0.0103
Gnomad4 AMR exome
AF:
0.000444
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000792
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000428
Gnomad4 OTH exome
AF:
0.000733
GnomAD4 genome
AF:
0.00259
AC:
286
AN:
110621
Hom.:
3
Cov.:
21
AF XY:
0.00240
AC XY:
79
AN XY:
32859
show subpopulations
Gnomad4 AFR
AF:
0.00881
Gnomad4 AMR
AF:
0.00132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000379
Gnomad4 OTH
AF:
0.00133
Alfa
AF:
0.00221
Hom.:
5
Bravo
AF:
0.00265
ExAC
AF:
0.000163
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

See cases Benign:1
Sep 01, 2021
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ACMG classification criteria: BS2, BP4 -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.80
T
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.1
DANN
Benign
0.69
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.29
T
MetaRNN
Benign
0.0036
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.11
N
REVEL
Benign
0.028
Sift
Pathogenic
0.0
D
Vest4
0.057
MutPred
0.085
Loss of helix (P = 0.079);
MVP
0.29
ClinPred
0.0063
T
GERP RS
-0.85
gMVP
0.072

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.

Other links and lift over

dbSNP: rs138128701; hg19: chrX-150565362; API