X-150671507-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_000252.3(MTM1):c.1724A>G(p.Gln575Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,208,938 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q575P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000252.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.1724A>G | p.Gln575Arg | missense_variant | 15/15 | ENST00000370396.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTM1 | ENST00000370396.7 | c.1724A>G | p.Gln575Arg | missense_variant | 15/15 | 1 | NM_000252.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000180 AC: 2AN: 110870Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33060
GnomAD4 exome AF: 0.0000109 AC: 12AN: 1098068Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 4AN XY: 363432
GnomAD4 genome ? AF: 0.0000180 AC: 2AN: 110870Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33060
ClinVar
Submissions by phenotype
Severe X-linked myotubular myopathy Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | May 20, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces glutamine with arginine at codon 575 of the MTM1 protein (p.Gln575Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MTM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 530853). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 10, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at