Variant X-67545316-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-TGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000044.6(AR):c.234_239del(p.Gln79_Gln80del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 972,753 control chromosomes in the GnomAD database, including 578 homozygotes. There are 3,759 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 412 hom., 660 hem., cov: 0)

Exomes 𝑓: 0.031 ( 166 hom. 3099 hem. )

Consequence

AR
NM_000044.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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-TGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCA-T is described in ClinVar as [Benign]. Clinvar id is 1276845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-67545316-TGCAGCA-T is described in Lovd as [Likely_benign]. Variant chrX-67545316-TGCAGCA-T is described in Lovd as [Benign]. Variant chrX-67545316-TGCAGCA-T is described in Lovd as [Benign]. Variant chrX-67545316-TGCAGCA-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.234_239del	p.Gln79_Gln80del	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 linkuse as main transcript	c.234_239del	p.Gln79_Gln80del	inframe_deletion	1/8	1	NM_000044.6	ENSP00000363822	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

7056

AN:

66528

Hom.:

415

Cov.:

AF XY:

0.0803

AC XY:

660

AN XY:

8216

show subpopulations

Gnomad AFR

AF:

0.0781

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0981

Gnomad EAS

AF:

0.0686

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.157

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.0900

GnomAD4 exome

AF:

0.0305

AC:

27642

AN:

906238

Hom.:

166

AF XY:

0.0115

AC XY:

3099

AN XY:

268732

show subpopulations

Gnomad4 AFR exome

AF:

0.0310

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.0443

Gnomad4 EAS exome

AF:

0.0413

Gnomad4 SAS exome

AF:

0.0356

Gnomad4 FIN exome

AF:

0.0934

Gnomad4 NFE exome

AF:

0.0260

Gnomad4 OTH exome

AF:

0.0416

GnomAD4 genome

AF:

0.106

AC:

7049

AN:

66515

Hom.:

412

Cov.:

AF XY:

0.0802

AC XY:

660

AN XY:

8229

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.0723

Gnomad4 ASJ

AF:

0.0981

Gnomad4 EAS

AF:

0.0684

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.0889

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 16, 2019	- -

not specified

Benign:1

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

Aug 29, 2023

- -

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.

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