rs201354330
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002206.3(ITGA7):c.2909C>T(p.Ala970Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A970T) has been classified as Uncertain significance.
Frequency
Consequence
NM_002206.3 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 | UniProt |
---|---|---|---|---|---|---|---|
ITGA7 | NM_002206.3 | c.2909C>T | p.Ala970Val | missense_variant | 22/25 | ENST00000257879.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA7 | ENST00000257879.11 | c.2909C>T | p.Ala970Val | missense_variant | 22/25 | 1 | NM_002206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152068Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251452Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461798Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 727216
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152068Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74298
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 970 of the ITGA7 protein (p.Ala970Val). This variant is present in population databases (rs201354330, gnomAD 0.02%). 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: 373222). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine 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 | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 18, 2016 | The A970V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The A970V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and Valine has been observed at this position in evolution. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at