X-67546514-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000044.6(AR):c.1415_1420dupGCGGCG(p.Gly472_Gly473dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000044.6 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AR | NM_000044.6 | c.1415_1420dupGCGGCG | p.Gly472_Gly473dup | disruptive_inframe_insertion | Exon 1 of 8 | ENST00000374690.9 | NP_000035.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0284 AC: 2360AN: 83019Hom.: 54 Cov.: 0 AF XY: 0.0196 AC XY: 325AN XY: 16609
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0170 AC: 8096AN: 475254Hom.: 147 Cov.: 25 AF XY: 0.0161 AC XY: 1890AN XY: 117724
GnomAD4 genome AF: 0.0285 AC: 2363AN: 83023Hom.: 54 Cov.: 0 AF XY: 0.0196 AC XY: 325AN XY: 16619
ClinVar
Submissions by phenotype
not specified Benign:2
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Variant summary: AR c.1415_1420dupGCGGCG (p.Gly472_Gly473dup) results in an in-frame duplication that is predicted to duplicate two amino acids into the encoded protein. The variant allele was found at a frequency of 0.019 in 558277 control chromosomes in the gnomAD database, including 201 homozygotes. The observed variant frequency is above the estimated maximal expected allele frequency for a pathogenic variant in AR causing Androgen Resistance Syndrome strongly suggesting that the variant is benign. c.1415_1420dupGCGGCG has been reported in the literature in an individual affected with Androgen Resistance Syndrome (Wu_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29693241). ClinVar contains an entry for this variant (Variation ID: 434265). Based on the evidence outlined above, the variant was classified as benign. -
Androgen resistance syndrome;C1839259:Kennedy disease Benign:1
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not provided Benign:1
AR: BS1, BS2 -
Androgen resistance syndrome;C0268301:Partial androgen insensitivity syndrome;C0376358:Malignant tumor of prostate;C1839259:Kennedy disease;C2678098:Hypospadias 1, X-linked Benign:1
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AR-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at