1-46196013-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017739.4(POMGNT1):c.419C>T(p.Thr140Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. T140A) has been classified as Uncertain significance.
Frequency
Consequence
NM_017739.4 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
POMGNT1 | NM_017739.4 | c.419C>T | p.Thr140Met | missense_variant, splice_region_variant | 5/22 | ENST00000371984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMGNT1 | ENST00000371984.8 | c.419C>T | p.Thr140Met | missense_variant, splice_region_variant | 5/22 | 1 | NM_017739.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251308Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135866
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727194
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3;C3150417:Autosomal recessive limb-girdle muscular dystrophy type 2O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 09, 2022 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 140 of the POMGNT1 protein (p.Thr140Met). This variant is present in population databases (rs766157232, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 569569). 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 disruptive. 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. - |
Muscle eye brain disease Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at