9-131504241-C-T
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001077365.2(POMT1):c.23C>T(p.Pro8Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001077365.2 missense
Scores
Clinical Significance
Conservation
Publications
- muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp
- myopathy caused by variation in POMT1Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- autosomal recessive limb-girdle muscular dystrophy type 2KInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- congenital muscular dystrophy with cerebellar involvementInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- congenital muscular dystrophy with intellectual disabilityInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- congenital muscular dystrophy without intellectual disabilityInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- muscle-eye-brain diseaseInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- muscular dystrophy-dystroglycanopathy, type AInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POMT1 | NM_001077365.2 | c.23C>T | p.Pro8Leu | missense_variant | Exon 2 of 20 | ENST00000402686.8 | NP_001070833.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727238 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Walker-Warburg congenital muscular dystrophy;C1836373:Autosomal recessive limb-girdle muscular dystrophy type 2K;C5436962:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 8 of the POMT1 protein (p.Pro8Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at