rs869320732
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000044.6(AR):c.2281_2287delinsTTCGCCCCTGA(p.Arg761PhefsTer9) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
AR
NM_000044.6 frameshift
NM_000044.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.05
Genes affected
AR (HGNC:644): (androgen receptor) The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-67717585-AGGATGC-TTCGCCCCTGA is Pathogenic according to our data. Variant chrX-67717585-AGGATGC-TTCGCCCCTGA is described in ClinVar as [Pathogenic]. Clinvar id is 9859.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.2281_2287delinsTTCGCCCCTGA | p.Arg761PhefsTer9 | frameshift_variant | 5/8 | ENST00000374690.9 | |
AR | NM_001011645.3 | c.685_691delinsTTCGCCCCTGA | p.Arg229PhefsTer9 | frameshift_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AR | ENST00000374690.9 | c.2281_2287delinsTTCGCCCCTGA | p.Arg761PhefsTer9 | frameshift_variant | 5/8 | 1 | NM_000044.6 | P1 | |
AR | ENST00000396044.8 | c.2173+5896_2173+5902delinsTTCGCCCCTGA | intron_variant | 1 | |||||
AR | ENST00000396043.4 | c.*629_*635delinsTTCGCCCCTGA | 3_prime_UTR_variant, NMD_transcript_variant | 6/9 | 1 | ||||
AR | ENST00000612452.5 | c.2281_2287delinsTTCGCCCCTGA | p.Arg761PhefsTer9 | frameshift_variant, NMD_transcript_variant | 5/9 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Androgen resistance syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at