NM_000208.4:c.3485C>A
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_000208.4(INSR):c.3485C>A(p.Ala1162Glu) 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. 13/22 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1162V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000208.4 missense
Scores
Clinical Significance
Conservation
Publications
- insulin-resistance syndrome type AInheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
- Donohue syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
- hyperinsulinism due to INSR deficiencyInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, Ambry Genetics
- Rabson-Mendenhall syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
Genome browser will be placed here
ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.3485C>A | p.Ala1162Glu | missense_variant | Exon 19 of 22 | ENST00000302850.10 | NP_000199.2 | |
INSR | NM_001079817.3 | c.3449C>A | p.Ala1150Glu | missense_variant | Exon 18 of 21 | NP_001073285.1 | ||
INSR | XM_011527988.3 | c.3482C>A | p.Ala1161Glu | missense_variant | Exon 19 of 22 | XP_011526290.2 | ||
INSR | XM_011527989.4 | c.3446C>A | p.Ala1149Glu | missense_variant | Exon 18 of 21 | XP_011526291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.3485C>A | p.Ala1162Glu | missense_variant | Exon 19 of 22 | 1 | NM_000208.4 | ENSP00000303830.4 | ||
INSR | ENST00000341500.9 | c.3449C>A | p.Ala1150Glu | missense_variant | Exon 18 of 21 | 1 | ENSP00000342838.4 | |||
INSR | ENST00000593970.1 | n.331C>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | |||||
INSR | ENST00000601099.1 | n.396C>A | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Insulin-resistant diabetes mellitus AND acanthosis nigricans Pathogenic:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at