19-7120739-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP2PP3_Strong
The NM_000208.4(INSR):c.3540G>A(p.Met1180Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000208.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.3540G>A | p.Met1180Ile | missense_variant | Exon 20 of 22 | ENST00000302850.10 | NP_000199.2 | |
INSR | NM_001079817.3 | c.3504G>A | p.Met1168Ile | missense_variant | Exon 19 of 21 | NP_001073285.1 | ||
INSR | XM_011527988.3 | c.3537G>A | p.Met1179Ile | missense_variant | Exon 20 of 22 | XP_011526290.2 | ||
INSR | XM_011527989.4 | c.3501G>A | p.Met1167Ile | missense_variant | Exon 19 of 21 | XP_011526291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.3540G>A | p.Met1180Ile | missense_variant | Exon 20 of 22 | 1 | NM_000208.4 | ENSP00000303830.4 | ||
INSR | ENST00000341500.9 | c.3504G>A | p.Met1168Ile | missense_variant | Exon 19 of 21 | 1 | ENSP00000342838.4 | |||
INSR | ENST00000601099.1 | n.451G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Insulin resistance Pathogenic:1
- -
not provided Uncertain:1
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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). Experimental studies have shown that this missense change affects INSR function (PMID: 1314826, 1890161). 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. ClinVar contains an entry for this variant (Variation ID: 14709). This sequence change replaces methionine with isoleucine at codon 1180 of the INSR protein (p.Met1180Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with INSR-related conditions (PMID: 1890161). This variant is also known as p.Met1153Ile. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at