chr3-165009359-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_001041.4(SI):āc.4099A>Gā(p.Arg1367Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000337 in 1,613,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001041.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SI | NM_001041.4 | c.4099A>G | p.Arg1367Gly | missense_variant | Exon 35 of 48 | ENST00000264382.8 | NP_001032.2 | |
SI | XM_047448735.1 | c.4099A>G | p.Arg1367Gly | missense_variant | Exon 36 of 49 | XP_047304691.1 | ||
SI | XM_047448736.1 | c.4099A>G | p.Arg1367Gly | missense_variant | Exon 36 of 49 | XP_047304692.1 | ||
SI | XM_011513078.3 | c.4000A>G | p.Arg1334Gly | missense_variant | Exon 34 of 47 | XP_011511380.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 66AN: 251028Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135682
GnomAD4 exome AF: 0.000338 AC: 494AN: 1461276Hom.: 0 Cov.: 30 AF XY: 0.000341 AC XY: 248AN XY: 726936
GnomAD4 genome AF: 0.000322 AC: 49AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74316
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
Identified in at least one patient with irritable bowel syndrome with diarrhea in published literature (Garcia-Etxebarria et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16329100, 29408290) -
This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1367 of the SI protein (p.Arg1367Gly). This variant is present in population databases (rs143388292, gnomAD 0.05%). This missense change has been observed in individual(s) with sucrase-isomaltase deficiency and irritable bowel syndrome (PMID: 16329100, 29408290, 32732636). ClinVar contains an entry for this variant (Variation ID: 344017). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SI protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Sucrase-isomaltase deficiency Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at