X-67545306-TTGC-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_000044.6(AR):βc.170_172delβ(p.Leu57del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,143,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.00050 ( 0 hom., 11 hem., cov: 19)
Exomes π: 0.000072 ( 0 hom. 8 hem. )
Consequence
AR
NM_000044.6 inframe_deletion
NM_000044.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.29
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 Likely_benign. Variant got -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_000044.6. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High Hemizygotes in GnomAd4 at 11 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.170_172del | p.Leu57del | inframe_deletion | 1/8 | ENST00000374690.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AR | ENST00000374690.9 | c.170_172del | p.Leu57del | inframe_deletion | 1/8 | 1 | NM_000044.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000498 AC: 41AN: 82409Hom.: 0 Cov.: 19 AF XY: 0.000642 AC XY: 11AN XY: 17137
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GnomAD3 exomes AF: 0.0000944 AC: 15AN: 158966Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 57580
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GnomAD4 exome AF: 0.0000716 AC: 76AN: 1061221Hom.: 0 AF XY: 0.0000233 AC XY: 8AN XY: 343591
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GnomAD4 genome AF: 0.000497 AC: 41AN: 82428Hom.: 0 Cov.: 19 AF XY: 0.000641 AC XY: 11AN XY: 17160
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2021 | This variant is associated with the following publications: (PMID: 23044881, 16172197) - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at