rs140530307
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_003977.4(AIP):c.382C>T(p.Arg128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R128H) has been classified as Likely benign.
Frequency
Consequence
NM_003977.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIP | NM_003977.4 | c.382C>T | p.Arg128Cys | missense_variant | 3/6 | ENST00000279146.8 | |
AIP | NM_001302960.2 | c.382C>T | p.Arg128Cys | missense_variant | 3/6 | ||
AIP | NM_001302959.2 | c.205C>T | p.Arg69Cys | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIP | ENST00000279146.8 | c.382C>T | p.Arg128Cys | missense_variant | 3/6 | 1 | NM_003977.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000493 AC: 75AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000132 AC: 33AN: 249898Hom.: 0 AF XY: 0.0000811 AC XY: 11AN XY: 135606
GnomAD4 exome AF: 0.0000548 AC: 80AN: 1460586Hom.: 0 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 726618
GnomAD4 genome ? AF: 0.000492 AC: 75AN: 152344Hom.: 0 Cov.: 33 AF XY: 0.000497 AC XY: 37AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 25, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 20, 2021 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 19, 2021 | - - |
Somatotroph adenoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 19, 2024 | - - |
Familial isolated pituitary adenoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Aug 05, 2021 | The AIP c.382C>T (p.Arg128Cys) missense change has a maximum subpopulation frequency of 0.19% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/11-67256840-C-T). In silico tools are not in agreement about the effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. This variant has been reported in individuals with pituitary adenomas (PS4_supporting; PMID: 26792934, 29074612), including two with acromegaly (PMID: 29074612). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PS4_supporting. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at