rs140642341
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_000252.3(MTM1):c.422C>T(p.Ala141Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000407 in 1,204,584 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A141P) has been classified as Uncertain significance.
Frequency
Consequence
NM_000252.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTM1 | NM_000252.3 | c.422C>T | p.Ala141Val | missense_variant | 6/15 | ENST00000370396.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTM1 | ENST00000370396.7 | c.422C>T | p.Ala141Val | missense_variant | 6/15 | 1 | NM_000252.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000807 AC: 9AN: 111487Hom.: 0 Cov.: 23 AF XY: 0.0000891 AC XY: 3AN XY: 33671
GnomAD3 exomes AF: 0.0000819 AC: 15AN: 183221Hom.: 0 AF XY: 0.000118 AC XY: 8AN XY: 67753
GnomAD4 exome AF: 0.0000366 AC: 40AN: 1093042Hom.: 0 Cov.: 29 AF XY: 0.0000502 AC XY: 18AN XY: 358560
GnomAD4 genome ? AF: 0.0000807 AC: 9AN: 111542Hom.: 0 Cov.: 23 AF XY: 0.0000889 AC XY: 3AN XY: 33736
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 27, 2021 | The c.422C>T (p.A141V) alteration is located in exon 6 (coding exon 5) of the MTM1 gene. This alteration results from a C to T substitution at nucleotide position 422, causing the alanine (A) at amino acid position 141 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 10, 2015 | - - |
Severe X-linked myotubular myopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2022 | MTM1: BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at