rs368933035
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_003977.4(AIP):c.355C>T(p.Arg119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R119Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003977.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIP | NM_003977.4 | c.355C>T | p.Arg119Trp | missense_variant | 3/6 | ENST00000279146.8 | |
AIP | NM_001302960.2 | c.355C>T | p.Arg119Trp | missense_variant | 3/6 | ||
AIP | NM_001302959.2 | c.178C>T | p.Arg60Trp | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIP | ENST00000279146.8 | c.355C>T | p.Arg119Trp | missense_variant | 3/6 | 1 | NM_003977.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249342Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135400
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460198Hom.: 0 Cov.: 32 AF XY: 0.0000427 AC XY: 31AN XY: 726390
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74370
ClinVar
Submissions by phenotype
Somatotroph adenoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 22, 2024 | - - |
Pituitary dependent hypercortisolism;C4538355:Somatotroph adenoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 17, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 119 of the AIP protein (p.Arg119Trp). This variant is present in population databases (rs368933035, gnomAD 0.007%). This missense change has been observed in individual(s) with pituitary adenoma (PMID: 24050928). ClinVar contains an entry for this variant (Variation ID: 485072). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2024 | The p.R119W variant (also known as c.355C>T), located in coding exon 3 of the AIP gene, results from a C to T substitution at nucleotide position 355. The arginine at codon 119 is replaced by tryptophan, an amino acid with dissimilar properties. In a study of Han Chinese patients with pituitary adenomas, this variant was observed in 1/216 sporadic pituitary adenoma patients and was not seen in the 6 familial pituitary adenoma families or in 100 unrelated healthy controls. This patient was 32 year old female diagnosed with an aggressive growth hormone secreting adenoma (Cai F et al. Eur. J. Endocrinol. 2013 Dec;169:867-84). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at