chr1-154925142-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting
The NM_006556.4(PMVK):c.566G>A(p.Arg189His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,611,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R189C) has been classified as Uncertain significance.
Frequency
Consequence
NM_006556.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMVK | NM_006556.4 | c.566G>A | p.Arg189His | missense_variant | Exon 5 of 5 | ENST00000368467.4 | NP_006547.1 | |
PMVK | NM_001323011.3 | c.524G>A | p.Arg175His | missense_variant | Exon 5 of 5 | NP_001309940.1 | ||
PMVK | NM_001323012.3 | c.341G>A | p.Arg114His | missense_variant | Exon 5 of 5 | NP_001309941.1 | ||
PMVK | NM_001348696.2 | c.341G>A | p.Arg114His | missense_variant | Exon 5 of 5 | NP_001335625.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000465 AC: 7AN: 150486Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251428Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135886
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461484Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 16AN XY: 727056
GnomAD4 genome AF: 0.0000465 AC: 7AN: 150486Hom.: 0 Cov.: 31 AF XY: 0.0000409 AC XY: 3AN XY: 73288
ClinVar
Submissions by phenotype
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at