NM_181882.3:c.1129G>T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_181882.3(PRX):c.1129G>T(p.Val377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V377V) has been classified as Likely benign.
Frequency
Consequence
NM_181882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.1129G>T | p.Val377Leu | missense_variant | Exon 7 of 7 | ENST00000324001.8 | NP_870998.2 | |
PRX | NM_001411127.1 | c.1414G>T | p.Val472Leu | missense_variant | Exon 7 of 7 | NP_001398056.1 | ||
PRX | XM_017027047.2 | c.1027G>T | p.Val343Leu | missense_variant | Exon 4 of 4 | XP_016882536.1 | ||
PRX | NM_020956.2 | c.*1334G>T | 3_prime_UTR_variant | Exon 6 of 6 | NP_066007.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000156 AC: 39AN: 250384Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135668
GnomAD4 exome AF: 0.0000807 AC: 118AN: 1461646Hom.: 0 Cov.: 36 AF XY: 0.0000976 AC XY: 71AN XY: 727152
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Charcot-Marie-Tooth disease Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at