chr9-124482765-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_004959.5(NR5A1):c.1379A>C(p.Gln460Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,298,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q460R) has been classified as Uncertain significance.
Frequency
Consequence
NM_004959.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR5A1 | NM_004959.5 | c.1379A>C | p.Gln460Pro | missense_variant | 7/7 | ENST00000373588.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR5A1 | ENST00000373588.9 | c.1379A>C | p.Gln460Pro | missense_variant | 7/7 | 1 | NM_004959.5 | P1 | |
NR5A1 | ENST00000620110.4 | c.1259A>C | p.Gln420Pro | missense_variant | 6/6 | 5 | |||
NR5A1 | ENST00000373587.3 | c.731A>C | p.Gln244Pro | missense_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000108 AC: 14AN: 129820Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.000109 AC: 19AN: 174450Hom.: 0 AF XY: 0.000139 AC XY: 13AN XY: 93254
GnomAD4 exome AF: 0.000149 AC: 174AN: 1168594Hom.: 0 Cov.: 38 AF XY: 0.000158 AC XY: 91AN XY: 574570
GnomAD4 genome AF: 0.000108 AC: 14AN: 129868Hom.: 0 Cov.: 29 AF XY: 0.0000976 AC XY: 6AN XY: 61470
ClinVar
Submissions by phenotype
Oligosynaptic infertility;C2751824:46,XY disorder of sex development Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 460 of the NR5A1 protein (p.Gln460Pro). This variant is present in population databases (rs146454575, gnomAD 0.02%). This missense change has been observed in individual(s) with 46XY sex reversal (Invitae). 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 disrupts the p.Gln460 amino acid residue in NR5A1. Other variant(s) that disrupt this residue have been observed in individuals with NR5A1-related conditions (PMID: 29935645; Invitae), which suggests that this may be a clinically significant amino acid residue. 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. - |
Male infertility Uncertain:1
Uncertain significance, criteria provided, single submitter | in vitro;research | Institute of Reproductive Genetics, University of Münster | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at