X-151397033-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001363810.1(VMA21):​c.194G>T​(p.Gly65Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 389,199 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 21)
Exomes 𝑓: 0.000023 ( 0 hom. 3 hem. )

Consequence

VMA21
NM_001363810.1 missense

Scores

2
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.984
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07777944).
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VMA21NM_001363810.1 linkc.194G>T p.Gly65Val 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.194G>T p.Gly65Val missense_variant Exon 2 of 4 5 ENSP00000359386.1 Q3ZAQ7-2
ENSG00000287918ENST00000660681.2 linkn.105C>A non_coding_transcript_exon_variant Exon 1 of 2
ENSG00000287918ENST00000668689.1 linkn.110C>A non_coding_transcript_exon_variant Exon 1 of 2

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD3 exomes
AF:
0.0000237
AC:
2
AN:
84537
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
26317
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000153
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000322
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000231
AC:
9
AN:
389199
Hom.:
0
Cov.:
0
AF XY:
0.0000219
AC XY:
3
AN XY:
136977
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000340
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000446
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
2.2
DANN
Uncertain
0.98
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.078
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
0.070
N
REVEL
Benign
0.0010
Sift
Uncertain
0.011
D
Sift4G
Benign
0.19
T
Vest4
0.073
MutPred
0.26
Gain of sheet (P = 0.0016);
MVP
0.35
ClinPred
0.022
T
GERP RS
-0.93
gMVP
0.49

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: rs753376606; hg19: chrX-150565505; API