GeneBe

rs3032358

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_000044.6(AR):​c.186_239delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA​(p.Gln63_Gln80del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000533 in 937,336 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000053 ( 0 hom. 0 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40

Publications

0 publications found
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]
AR Gene-Disease associations (from GenCC):
  • androgen insensitivity syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
  • Kennedy disease
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • partial androgen insensitivity syndrome
    Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
  • complete androgen insensitivity syndrome
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_000044.6

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARNM_000044.6 linkc.186_239delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln63_Gln80del disruptive_inframe_deletion 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.186_239delGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA p.Gln63_Gln80del disruptive_inframe_deletion Exon 1 of 8 1 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.00000533
AC:
5
AN:
937336
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
295426
show subpopulations
African (AFR)
AF:
0.0000421
AC:
1
AN:
23762
American (AMR)
AF:
0.00
AC:
0
AN:
25862
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16269
East Asian (EAS)
AF:
0.00
AC:
0
AN:
28387
South Asian (SAS)
AF:
0.00
AC:
0
AN:
45251
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36191
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2596
European-Non Finnish (NFE)
AF:
0.00000278
AC:
2
AN:
719116
Other (OTH)
AF:
0.0000501
AC:
2
AN:
39902
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.565
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.4

Splicing

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

Publications

Other links and lift over

dbSNP: rs3032358; hg19: chrX-66765158; API