Variant X-67546514-T-TGGCGGCGGCGGCGGCGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000044.6(AR):c.1403_1420dup(p.Gly468_Gly473dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. G456G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., 11 hem., cov: 0)

Exomes 𝑓: 0.000031 ( 0 hom. 8 hem. )

Failed GnomAD Quality Control

Consequence

AR
NM_000044.6 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.29

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 Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AR	NM_000044.6 linkuse as main transcript	c.1403_1420dup	p.Gly468_Gly473dup	inframe_insertion	1/8	ENST00000374690.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AR	ENST00000374690.9 linkuse as main transcript	c.1403_1420dup	p.Gly468_Gly473dup	inframe_insertion	1/8	1	NM_000044.6	P1	P10275-1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

AN:

83056

Hom.:

Cov.:

AF XY:

0.000662

AC XY:

AN XY:

16622

show subpopulations

Gnomad AFR

AF:

0.00194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00102

Gnomad ASJ

AF:

0.000450

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00131

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000788

Gnomad OTH

AF:

0.000943

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000315

AC:

AN:

476300

Hom.:

Cov.:

AF XY:

0.0000676

AC XY:

AN XY:

118280

show subpopulations

Gnomad4 AFR exome

AF:

0.0000756

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000679

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000349

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00106

AC:

AN:

83060

Hom.:

Cov.:

AF XY:

0.000661

AC XY:

AN XY:

16632

show subpopulations

Gnomad4 AFR

AF:

0.00194

Gnomad4 AMR

AF:

0.00102

Gnomad4 ASJ

AF:

0.000450

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00131

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000788

Gnomad4 OTH

AF:

0.000929

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AR-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2024

The AR c.1403_1420dup18 variant is predicted to result in an in-frame duplication (p.Gly468_Gly473dup). To our knowledge, this variant has not been reported in the literature or in a large population database. However, the allele frequency of variant in gnomAD is not reliable due to the repetitive nature of the affected region. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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