chr10-5205767-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001818.5(AKR1C4):c.380C>T(p.Thr127Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,612,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001818.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKR1C4 | NM_001818.5 | c.380C>T | p.Thr127Met | missense_variant | 4/9 | ENST00000263126.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKR1C4 | ENST00000263126.3 | c.380C>T | p.Thr127Met | missense_variant | 4/9 | 1 | NM_001818.5 | P1 | |
AKR1C4 | ENST00000380448.5 | c.380C>T | p.Thr127Met | missense_variant | 6/11 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000479 AC: 12AN: 250434Hom.: 0 AF XY: 0.0000517 AC XY: 7AN XY: 135332
GnomAD4 exome AF: 0.0000479 AC: 70AN: 1460732Hom.: 0 Cov.: 30 AF XY: 0.0000454 AC XY: 33AN XY: 726680
GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74436
ClinVar
Submissions by phenotype
AKR1C4-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 18, 2024 | The AKR1C4 c.380C>T variant is predicted to result in the amino acid substitution p.Thr127Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | This variant has not been reported in the literature in individuals affected with AKR1C4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant is present in population databases (rs531165422, gnomAD 0.04%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 127 of the AKR1C4 protein (p.Thr127Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at