rs369489033
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_013382.7(POMT2):c.1141T>C(p.Tyr381His) variant causes a missense change. The variant allele was found at a frequency of 0.000228 in 1,396,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. Y381C) has been classified as Uncertain significance.
Frequency
Consequence
NM_013382.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.1141T>C | p.Tyr381His | missense_variant | 10/21 | ENST00000261534.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.1141T>C | p.Tyr381His | missense_variant | 10/21 | 1 | NM_013382.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000819 AC: 10AN: 122170Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000486 AC: 12AN: 247094Hom.: 0 AF XY: 0.0000374 AC XY: 5AN XY: 133580
GnomAD4 exome AF: 0.000242 AC: 308AN: 1274394Hom.: 0 Cov.: 34 AF XY: 0.000225 AC XY: 142AN XY: 631844
GnomAD4 genome ? AF: 0.0000819 AC: 10AN: 122170Hom.: 0 Cov.: 30 AF XY: 0.0000529 AC XY: 3AN XY: 56734
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 30, 2023 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 01, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 30, 2017 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 381 of the POMT2 protein (p.Tyr381His). This variant is present in population databases (rs369489033, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with POMT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 500176). 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.1141T>C (p.Y381H) alteration is located in exon 10 (coding exon 10) of the POMT2 gene. This alteration results from a T to C substitution at nucleotide position 1141, causing the tyrosine (Y) at amino acid position 381 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at