X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Position:

chrX-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

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]

AR links:

Genome browser will be placed here

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
AR	NM_000044.6 link	c.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
AR	ENST00000374690.9 link	c.237_239delGCA	p.Gln80del	disruptive_inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

10163

AN:

66458

Hom.:

753

Cov.:

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.:

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 provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2025

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

This 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 submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over