rs267606580

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The ENST00000279146.8(AIP):​c.824dup​(p.His275GlnfsTer13) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. H275H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

AIP
ENST00000279146.8 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 7.09
Variant links:
Genes affected
AIP (HGNC:358): (aryl hydrocarbon receptor interacting protein) The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-67490823-C-CA is Pathogenic according to our data. Variant chr11-67490823-C-CA is described in ClinVar as [Pathogenic]. Clinvar id is 4890.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AIPNM_003977.4 linkuse as main transcriptc.824dup p.His275GlnfsTer13 frameshift_variant 6/6 ENST00000279146.8 NP_003968.3
AIPNM_001302959.2 linkuse as main transcriptc.647dup p.His216GlnfsTer13 frameshift_variant 6/6 NP_001289888.1
AIPNM_001302960.2 linkuse as main transcriptc.816dup p.Arg273ThrfsTer28 frameshift_variant 6/6 NP_001289889.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AIPENST00000279146.8 linkuse as main transcriptc.824dup p.His275GlnfsTer13 frameshift_variant 6/61 NM_003977.4 ENSP00000279146 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Somatotroph adenoma Pathogenic:1Other:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMar 06, 2007- -
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs267606580; hg19: chr11-67258294; API