X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000044.6(AR):c.201_239dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln68_Gln80dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., 1 hem., cov: 0)
Exomes 𝑓: 0.000069 ( 0 hom. 10 hem. )
Failed GnomAD Quality Control
Consequence
AR
NM_000044.6 disruptive_inframe_insertion
NM_000044.6 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.337
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.201_239dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln68_Gln80dup | disruptive_inframe_insertion | 1/8 | ENST00000374690.9 | NP_000035.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000240 AC: 16AN: 66636Hom.: 0 Cov.: 0 AF XY: 0.000121 AC XY: 1AN XY: 8246
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000694 AC: 65AN: 937273Hom.: 0 Cov.: 40 AF XY: 0.0000339 AC XY: 10AN XY: 295385
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GnomAD4 genome AF: 0.000240 AC: 16AN: 66623Hom.: 0 Cov.: 0 AF XY: 0.000121 AC XY: 1AN XY: 8259
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Malignant tumor of prostate;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 15, 2021 | - - |
Kennedy disease Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | GeneReviews | Jan 26, 2017 | - - |
AR-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 16, 2024 | The AR c.201_239dup39 variant is predicted to result in an in-frame duplication (p.Gln68_Gln80dup). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at