rs77917609
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_181882.3(PRX):c.719G>A(p.Arg240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,543,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R240W) has been classified as Uncertain significance.
Frequency
Consequence
NM_181882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.719G>A | p.Arg240Gln | missense_variant | 7/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.1004G>A | p.Arg335Gln | missense_variant | 7/7 | ||
PRX | XM_017027047.2 | c.617G>A | p.Arg206Gln | missense_variant | 4/4 | ||
PRX | NM_020956.2 | c.*924G>A | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.719G>A | p.Arg240Gln | missense_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00126 AC: 192AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000314 AC: 44AN: 140038Hom.: 0 AF XY: 0.000221 AC XY: 17AN XY: 76808
GnomAD4 exome AF: 0.000145 AC: 201AN: 1390822Hom.: 0 Cov.: 35 AF XY: 0.000132 AC XY: 91AN XY: 686936
GnomAD4 genome AF: 0.00126 AC: 192AN: 152318Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96AN XY: 74476
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2019 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2021 | - - |
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at