X-67546589-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000044.6(AR):c.1443C>T(p.Tyr481=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,163,206 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0000092 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 0.000031 ( 0 hom. 14 hem. )
Consequence
AR
NM_000044.6 synonymous
NM_000044.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.174
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 -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant X-67546589-C-T is Benign according to our data. Variant chrX-67546589-C-T is described in ClinVar as [Benign]. Clinvar id is 2925268.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-67546589-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.174 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.1443C>T | p.Tyr481= | synonymous_variant | 1/8 | ENST00000374690.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AR | ENST00000374690.9 | c.1443C>T | p.Tyr481= | synonymous_variant | 1/8 | 1 | NM_000044.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000924 AC: 1AN: 108260Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 31262
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GnomAD3 exomes AF: 0.0000580 AC: 7AN: 120626Hom.: 0 AF XY: 0.0000853 AC XY: 3AN XY: 35180
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GnomAD4 exome AF: 0.0000313 AC: 33AN: 1054946Hom.: 0 Cov.: 34 AF XY: 0.0000413 AC XY: 14AN XY: 338660
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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 submitter | clinical testing | Invitae | Oct 07, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at