X-67545316-TGCAGCA-T

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_239delGCAGCA(p.Gln79_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 0.0357 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q78Q) has been classified as Likely 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.40

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-TGCAGCA-T is Benign according to our data. Variant chrX-67545316-TGCAGCA-T is described in ClinVar as Benign. ClinVar VariationId is 1276845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 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_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	NP_000035.2
AR	NM_001348063.1		c.234_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 4	NP_001334992.1	Q9NUA2
AR	NM_001348061.1		c.234_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	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_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 8	ENSP00000363822.3	P10275-1
AR	ENST00000396044.8	TSL:1	c.234_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 5	ENSP00000379359.3	F5GZG9
AR	ENST00000504326.5	TSL:1	c.234_239delGCAGCA	p.Gln79_Gln80del	disruptive_inframe_deletion	Exon 1 of 4	ENSP00000421155.1	P10275-3

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

7056

AN:

66528

Hom.:

415

Cov.:

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

African (AFR)

AF:

0.0310

AC:

720

AN:

23254

American (AMR)

AF:

0.0249

AC:

625

AN:

25077

Ashkenazi Jewish (ASJ)

AF:

0.0443

AC:

692

AN:

15632

East Asian (EAS)

AF:

0.0413

AC:

1116

AN:

27015

South Asian (SAS)

AF:

0.0356

AC:

1478

AN:

41505

European-Finnish (FIN)

AF:

0.0934

AC:

3167

AN:

33917

Middle Eastern (MID)

AF:

0.0389

AC:

AN:

2469

European-Non Finnish (NFE)

AF:

0.0260

AC:

18154

AN:

699052

Other (OTH)

AF:

0.0416

AC:

1594

AN:

38317

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

1268

2536

3804

5072

6340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.106

AC:

7049

AN:

66515

Hom.:

412

Cov.:

AF XY:

0.0802

AC XY:

660

AN XY:

8229

show subpopulations

African (AFR)

AF:

0.0780

AC:

1465

AN:

18774

American (AMR)

AF:

0.0723

AC:

378

AN:

5227

Ashkenazi Jewish (ASJ)

AF:

0.0981

AC:

168

AN:

1713

East Asian (EAS)

AF:

0.0684

AC:

126

AN:

1841

South Asian (SAS)

AF:

0.124

AC:

112

AN:

901

European-Finnish (FIN)

AF:

0.110

AC:

221

AN:

2014

Middle Eastern (MID)

AF:

0.158

AC:

AN:

133

European-Non Finnish (NFE)

AF:

0.128

AC:

4442

AN:

34656

Other (OTH)

AF:

0.0889

AC:

AN:

810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

254

509

763

1018

1272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0586

Hom.:

237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Androgen resistance syndrome;C1839259:Kennedy disease (1)

Kennedy disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=200/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over