rs201217064
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4_StrongBS2_Supporting
The NM_000298.6(PKLR):c.1614A>T(p.Glu538Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,613,966 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000298.6 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKLR | NM_000298.6 | c.1614A>T | p.Glu538Asp | missense_variant | 10/11 | ENST00000342741.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKLR | ENST00000342741.6 | c.1614A>T | p.Glu538Asp | missense_variant | 10/11 | 1 | NM_000298.6 | P3 | |
PKLR | ENST00000392414.7 | c.1521A>T | p.Glu507Asp | missense_variant | 10/11 | 1 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000520 AC: 79AN: 152002Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000398 AC: 100AN: 251484Hom.: 1 AF XY: 0.000375 AC XY: 51AN XY: 135922
GnomAD4 exome AF: 0.000292 AC: 427AN: 1461846Hom.: 2 Cov.: 33 AF XY: 0.000278 AC XY: 202AN XY: 727226
GnomAD4 genome AF: 0.000519 AC: 79AN: 152120Hom.: 0 Cov.: 31 AF XY: 0.000753 AC XY: 56AN XY: 74372
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 29, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2017 | The E538D variant in the PKLR gene has been reported previously in the heterozygous state in a single individual, however, it was not stated if this variant was found in trans with a second PKLR variant, and no phenotypic information was provided (Manco et al., 2009). The E538D variant is observed in 55/25786 (0.21%) alleles from individuals of Finnish European background, including one homozygous individual, in the ExAC dataset (Lek et al., 2016). The E538D variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E538D as a variant of uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 23, 2023 | - - |
Pyruvate kinase deficiency of red cells;C1863224:Pyruvate kinase hyperactivity Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at