X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_000044.6(AR):​c.1394_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCG​(p.Gly465_Gly473del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 559,145 control chromosomes in the GnomAD database, including 141 homozygotes. There are 483 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., 68 hem., cov: 0)
Exomes 𝑓: 0.0022 ( 140 hom. 415 hem. )

Consequence

AR
NM_000044.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B: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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is described in ClinVar as [Benign]. Clinvar id is 1600106.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGC-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00343 (285/83055) while in subpopulation AFR AF= 0.0114 (247/21648). AF 95% confidence interval is 0.0102. There are 1 homozygotes in gnomad4. There are 68 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 68 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARNM_000044.6 linkc.1394_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly465_Gly473del disruptive_inframe_deletion 1/8 ENST00000374690.9 NP_000035.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARENST00000374690.9 linkc.1394_1420delGCGGCGGCGGCGGCGGCGGCGGCGGCG p.Gly465_Gly473del disruptive_inframe_deletion 1/81 NM_000044.6 ENSP00000363822.3 P10275-1

Frequencies

GnomAD3 genomes
AF:
0.00343
AC:
285
AN:
83051
Hom.:
1
Cov.:
0
AF XY:
0.00409
AC XY:
68
AN XY:
16615
show subpopulations
Gnomad AFR
AF:
0.0114
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00154
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000388
Gnomad SAS
AF:
0.0111
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000943
GnomAD4 exome
AF:
0.00223
AC:
1062
AN:
476090
Hom.:
140
AF XY:
0.00351
AC XY:
415
AN XY:
118166
show subpopulations
Gnomad4 AFR exome
AF:
0.0196
Gnomad4 AMR exome
AF:
0.00291
Gnomad4 ASJ exome
AF:
0.000105
Gnomad4 EAS exome
AF:
0.00107
Gnomad4 SAS exome
AF:
0.0345
Gnomad4 FIN exome
AF:
0.000183
Gnomad4 NFE exome
AF:
0.000519
Gnomad4 OTH exome
AF:
0.00262
GnomAD4 genome
AF:
0.00343
AC:
285
AN:
83055
Hom.:
1
Cov.:
0
AF XY:
0.00409
AC XY:
68
AN XY:
16625
show subpopulations
Gnomad4 AFR
AF:
0.0114
Gnomad4 AMR
AF:
0.00154
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000390
Gnomad4 SAS
AF:
0.0112
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000929

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 17, 2024- -

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.

Other links and lift over

dbSNP: rs746853821; hg19: chrX-66766356; API