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Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000044.6(AR):​c.237_239delGCA​(p.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 0.0492 in 981,829 control chromosomes in the GnomAD database, including 1,031 homozygotes. There are 4,595 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 753 hom., 775 hem., cov: 0)
Exomes 𝑓: 0.042 ( 278 hom. 3820 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.40
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant X-67545316-TGCA-T is Benign according to our data. Variant chrX-67545316-TGCA-T is described in ClinVar as [Benign]. Clinvar id is 464798.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCA-T is described in Lovd as [Benign]. Variant chrX-67545316-TGCA-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARNM_000044.6 linkc.237_239delGCA p.Gln80del disruptive_inframe_deletion 1/8 ENST00000374690.9 NP_000035.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARENST00000374690.9 linkc.237_239delGCA p.Gln80del disruptive_inframe_deletion 1/81 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.153
AC:
10163
AN:
66458
Hom.:
753
Cov.:
0
AF XY:
0.0942
AC XY:
775
AN XY:
8228
show subpopulations
Gnomad AFR
AF:
0.110
Gnomad AMI
AF:
0.110
Gnomad AMR
AF:
0.145
Gnomad ASJ
AF:
0.117
Gnomad EAS
AF:
0.114
Gnomad SAS
AF:
0.101
Gnomad FIN
AF:
0.159
Gnomad MID
AF:
0.144
Gnomad NFE
AF:
0.183
Gnomad OTH
AF:
0.163
GnomAD4 exome
AF:
0.0417
AC:
38184
AN:
915384
Hom.:
278
AF XY:
0.0139
AC XY:
3820
AN XY:
274494
show subpopulations
Gnomad4 AFR exome
AF:
0.0376
Gnomad4 AMR exome
AF:
0.0519
Gnomad4 ASJ exome
AF:
0.0484
Gnomad4 EAS exome
AF:
0.0844
Gnomad4 SAS exome
AF:
0.0296
Gnomad4 FIN exome
AF:
0.120
Gnomad4 NFE exome
AF:
0.0356
Gnomad4 OTH exome
AF:
0.0575
GnomAD4 genome
AF:
0.153
AC:
10160
AN:
66445
Hom.:
753
Cov.:
0
AF XY:
0.0940
AC XY:
775
AN XY:
8241
show subpopulations
Gnomad4 AFR
AF:
0.109
Gnomad4 AMR
AF:
0.145
Gnomad4 ASJ
AF:
0.117
Gnomad4 EAS
AF:
0.115
Gnomad4 SAS
AF:
0.101
Gnomad4 FIN
AF:
0.159
Gnomad4 NFE
AF:
0.183
Gnomad4 OTH
AF:
0.161

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 08, 2025- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This variant is associated with the following publications: (PMID: 26398403) -
Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Malignant tumor of prostate;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked Benign:1
Benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsMay 04, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs3032358; hg19: chrX-66765158; API