GeneBe

rs193922933

Variant names:

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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 0.337
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.201_239dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln68_Gln80dup disruptive_inframe_insertion Exon 1 of 8 ENST00000374690.9 NP_000035.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARENST00000374690.9 linkc.201_239dupGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln68_Gln80dup disruptive_inframe_insertion Exon 1 of 8 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.000240
AC:
16
AN:
66636
Hom.:
0
Cov.:
0
AF XY:
0.000121
AC XY:
1
AN XY:
8246
show subpopulations
Gnomad AFR
AF:
0.000106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00162
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000288
Gnomad OTH
AF:
0.00125
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000694
AC:
65
AN:
937273
Hom.:
0
Cov.:
40
AF XY:
0.0000339
AC XY:
10
AN XY:
295385
show subpopulations
Gnomad4 AFR exome
AF:
0.0000842
Gnomad4 AMR exome
AF:
0.000271
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000663
Gnomad4 FIN exome
AF:
0.0000276
Gnomad4 NFE exome
AF:
0.0000556
Gnomad4 OTH exome
AF:
0.000150
GnomAD4 genome
AF:
0.000240
AC:
16
AN:
66623
Hom.:
0
Cov.:
0
AF XY:
0.000121
AC XY:
1
AN XY:
8259
show subpopulations
Gnomad4 AFR
AF:
0.000106
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00163
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000288
Gnomad4 OTH
AF:
0.00123

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
Jul 15, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Kennedy disease Uncertain:1
Jan 26, 2017
GeneReviews
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: literature only

- -

AR-related disorder Uncertain:1
Aug 16, 2024
PreventionGenetics, part of Exact Sciences
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs3032358; hg19: chrX-66765158; API