X-67723746-G-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PS1PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_000044.6(AR):c.2668G>T(p.Val890Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V890M) has been classified as Pathogenic.
Frequency
Consequence
NM_000044.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.2668G>T | p.Val890Leu | missense_variant | 8/8 | ENST00000374690.9 | |
AR | NM_001011645.3 | c.1072G>T | p.Val358Leu | missense_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AR | ENST00000374690.9 | c.2668G>T | p.Val890Leu | missense_variant | 8/8 | 1 | NM_000044.6 | P1 | |
AR | ENST00000396044.8 | c.*29G>T | 3_prime_UTR_variant | 5/5 | 1 | ||||
AR | ENST00000396043.4 | c.*1016G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/9 | 1 | ||||
AR | ENST00000612452.5 | c.2668G>T | p.Val890Leu | missense_variant, NMD_transcript_variant | 8/9 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 21
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 24, 2021 | DNA sequence analysis of the AR gene demonstrated a sequence change, c.2668G>T, in exon 8 that results in an amino acid change, p.Val890Leu. This sequence change is absent from known population databases (gnomAD). The p.Val890Leu change affects a highly conserved amino acid residue located in a domain of the AR protein that is known to be functional. The p.Val890Leu substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This particular sequence change (reported as p.Val889Leu) has been previously reported in individuals with AR-related disorders of sexual development (PMID: 20150575). A different pathogenic sequence change affecting the same amino acid residue (p.Val890Met, reported as p.Val889Met)) has also been described in individuals with AR-related disorders (PMID: 10425033). The p.Val890Leu amino acid change occurs in a region of the AR gene where other missense sequence changes have been described in patients with AR-related disorders. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.