14-24147703-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_017999.5(RNF31):c.5C>T(p.Pro2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000859 in 1,513,156 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 (★★).
Frequency
Consequence
NM_017999.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF31 | ENST00000324103.11 | c.5C>T | p.Pro2Leu | missense_variant | Exon 1 of 21 | 1 | NM_017999.5 | ENSP00000315112.6 | ||
ENSG00000259529 | ENST00000558468.2 | n.5C>T | non_coding_transcript_exon_variant | Exon 1 of 29 | 2 | ENSP00000457512.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000428 AC: 5AN: 116886Hom.: 0 AF XY: 0.0000155 AC XY: 1AN XY: 64568
GnomAD4 exome AF: 0.00000588 AC: 8AN: 1360908Hom.: 0 Cov.: 31 AF XY: 0.00000149 AC XY: 1AN XY: 670900
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74448
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.5C>T (p.P2L) alteration is located in exon 1 (coding exon 1) of the RNF31 gene. This alteration results from a C to T substitution at nucleotide position 5, causing the proline (P) at amino acid position 2 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1447265). This variant has not been reported in the literature in individuals affected with RNF31-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 2 of the RNF31 protein (p.Pro2Leu). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at