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, Laboratory for Molecular Medicine, G2P, Labcorp Genetics (formerly Invitae)
Kennedy disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Orphanet
partial androgen insensitivity syndrome
Inheritance: XL Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000044.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	NM_000044.6	MANE Select	c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 8	NP_000035.2
AR	NM_001348063.1		c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 4	NP_001334992.1	Q9NUA2
AR	NM_001348061.1		c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 4	NP_001334990.1	Q9NUA2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AR	ENST00000374690.9	TSL:1 MANE Select	c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 8	ENSP00000363822.3	P10275-1
AR	ENST00000396044.8	TSL:1	c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 5	ENSP00000379359.3	F5GZG9
AR	ENST00000504326.5	TSL:1	c.234_239dupGCAGCA	p.Gln79_Gln80dup	disruptive_inframe_insertion	Exon 1 of 4	ENSP00000421155.1	P10275-3

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (2)

Androgen resistance syndrome;C1839259:Kennedy disease (1)

Partial androgen insensitivity syndrome (1)

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over