X-151396898-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001363810.1(VMA21):c.59G>A(p.Cys20Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000977 in 522,075 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 38 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001363810.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VMA21 | NM_001363810.1 | c.59G>A | p.Cys20Tyr | missense_variant | Exon 1 of 3 | NP_001350739.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VMA21 | ENST00000370361.5 | c.59G>A | p.Cys20Tyr | missense_variant | Exon 2 of 4 | 5 | ENSP00000359386.1 | |||
ENSG00000287918 | ENST00000660681.2 | n.240C>T | non_coding_transcript_exon_variant | Exon 1 of 2 | ||||||
ENSG00000287918 | ENST00000664935.1 | n.121C>T | non_coding_transcript_exon_variant | Exon 1 of 2 |
Frequencies
GnomAD3 genomes AF: 0.0000181 AC: 2AN: 110321Hom.: 0 Cov.: 21 AF XY: 0.0000307 AC XY: 1AN XY: 32563
GnomAD3 exomes AF: 0.000117 AC: 12AN: 102579Hom.: 0 AF XY: 0.000160 AC XY: 6AN XY: 37389
GnomAD4 exome AF: 0.000119 AC: 49AN: 411754Hom.: 0 Cov.: 0 AF XY: 0.000244 AC XY: 37AN XY: 151836
GnomAD4 genome AF: 0.0000181 AC: 2AN: 110321Hom.: 0 Cov.: 21 AF XY: 0.0000307 AC XY: 1AN XY: 32563
ClinVar
Submissions by phenotype
X-linked myopathy with excessive autophagy Uncertain:1
The missense c.59G>A(p.Cys20Tyr) variant in VMA21 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.01% in the gnomAD and novel in 1000 genome. The amino acid Cys at position 20 is changed to a Tyr changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance. -
VMA21-related disorder Benign:1
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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at