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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000044.6(AR):c.213_239dup(p.Gln72_Gln80dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., 5 hem., cov: 0)

Exomes 𝑓: 0.00067 ( 0 hom. 42 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.337

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant X-67545316-T-TGCAGCAGCAGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chrX-67545316-T-TGCAGCAGCAGCAGCAGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 422605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AR	NM_000044.6 linkuse as main transcript	c.213_239dup	p.Gln72_Gln80dup	inframe_insertion	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.213_239dup	p.Gln72_Gln80dup	inframe_insertion	1/8	1	NM_000044.6	ENSP00000363822	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

119

AN:

66636

Hom.:

Cov.:

AF XY:

0.000606

AC XY:

AN XY:

8246

show subpopulations

Gnomad AFR

AF:

0.000852

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00306

Gnomad ASJ

AF:

0.00408

Gnomad EAS

AF:

0.00486

Gnomad SAS

AF:

0.00110

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00499

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000674

AC:

631

AN:

936887

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

295033

show subpopulations

Gnomad4 AFR exome

AF:

0.000463

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00301

Gnomad4 EAS exome

AF:

0.00332

Gnomad4 SAS exome

AF:

0.000819

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.000472

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00179

AC:

119

AN:

66623

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

8259

show subpopulations

Gnomad4 AFR

AF:

0.000851

Gnomad4 AMR

AF:

0.00306

Gnomad4 ASJ

AF:

0.00408

Gnomad4 EAS

AF:

0.00488

Gnomad4 SAS

AF:

0.00111

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00493

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Androgen resistance syndrome;C1839259:Kennedy disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 12, 2021

This variant is associated with the following publications: (PMID: 2062380) -

Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Malignant tumor of prostate;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 06, 2022

- -

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