rs749679578
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000257879.11(ITGA7):c.1982C>T(p.Thr661Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,605,470 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T661T) has been classified as Likely benign.
Frequency
Consequence
ENST00000257879.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITGA7 | NM_002206.3 | c.1982C>T | p.Thr661Met | missense_variant | 14/25 | ENST00000257879.11 | NP_002197.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITGA7 | ENST00000257879.11 | c.1982C>T | p.Thr661Met | missense_variant | 14/25 | 1 | NM_002206.3 | ENSP00000257879 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000199 AC: 3AN: 150420Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251444Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135908
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1455050Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 723840
GnomAD4 genome AF: 0.0000199 AC: 3AN: 150420Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 73306
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 661 of the ITGA7 protein (p.Thr661Met). This variant is present in population databases (rs749679578, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. ClinVar contains an entry for this variant (Variation ID: 470571). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 12, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 07, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at