X-67545316-T-TGCAGCA

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000044.6(AR):c.234_239dupGCAGCA(p.Gln79_Gln80dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0348 in 985,708 control chromosomes in the GnomAD database, including 2,458 homozygotes. There are 5,284 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. Q80Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.075 ( 390 hom., 382 hem., cov: 0)

Exomes 𝑓: 0.032 ( 2068 hom. 4902 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.337

Publications

10 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

AR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000044.6

BP6

Variant X-67545316-T-TGCAGCA is Benign according to our data. Variant chrX-67545316-T-TGCAGCA is described in ClinVar as Benign. ClinVar VariationId is 290422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AR	NM_000044.6 link	c.234_239dupGCAGCA	p.Gln79_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
AR	ENST00000374690.9 link	c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 8	1	NM_000044.6	ENSP00000363822.3		P10275-1

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

4999

AN:

66586

Hom.:

391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0371

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0931

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0941

Gnomad SAS

AF:

0.0844

Gnomad FIN

AF:

0.0549

Gnomad MID

AF:

0.0980

Gnomad NFE

AF:

0.0916

Gnomad OTH

AF:

0.0810

GnomAD4 exome

AF:

0.0319

AC:

29275

AN:

919135

Hom.:

2068

Cov.:

AF XY:

0.0176

AC XY:

4902

AN XY:

278389

show subpopulations

African (AFR)

AF:

0.0155

AC:

365

AN:

23588

American (AMR)

AF:

0.0649

AC:

1629

AN:

25112

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

890

AN:

15605

East Asian (EAS)

AF:

0.0822

AC:

2232

AN:

27160

South Asian (SAS)

AF:

0.0487

AC:

2061

AN:

42334

European-Finnish (FIN)

AF:

0.0592

AC:

2066

AN:

34916

Middle Eastern (MID)

AF:

0.0558

AC:

140

AN:

2508

European-Non Finnish (NFE)

AF:

0.0255

AC:

18068

AN:

708927

Other (OTH)

AF:

0.0468

AC:

1824

AN:

38985

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

1043

2086

3128

4171

5214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0750

AC:

4996

AN:

66573

Hom.:

390

Cov.:

AF XY:

0.0463

AC XY:

382

AN XY:

8249

show subpopulations

African (AFR)

AF:

0.0370

AC:

696

AN:

18796

American (AMR)

AF:

0.0929

AC:

486

AN:

5229

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

176

AN:

1715

East Asian (EAS)

AF:

0.0929

AC:

171

AN:

1840

South Asian (SAS)

AF:

0.0866

AC:

AN:

901

European-Finnish (FIN)

AF:

0.0549

AC:

111

AN:

2023

Middle Eastern (MID)

AF:

0.105

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.0916

AC:

3176

AN:

34678

Other (OTH)

AF:

0.0813

AC:

AN:

812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

175

350

524

699

874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0566

Hom.:

237

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jun 18, 2020

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 31, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Partial androgen insensitivity syndrome

Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

European Non-Finnish population allele frequency is 10.38% (rs78686797, 364/3209 alleles, 0 homozygotes, 3 hemizygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.3.2, this variant is classified as BENIGN. Following criteria are met: BA1 -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Sep 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=69/31

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over