chr16-8847737-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The ENST00000268261.9(PMM2):āc.653A>Gā(p.His218Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H218L) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000268261.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PMM2 | NM_000303.3 | c.653A>G | p.His218Arg | missense_variant | 8/8 | ENST00000268261.9 | NP_000294.1 | |
PMM2 | XM_047434215.1 | c.404A>G | p.His135Arg | missense_variant | 6/6 | XP_047290171.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PMM2 | ENST00000268261.9 | c.653A>G | p.His218Arg | missense_variant | 8/8 | 1 | NM_000303.3 | ENSP00000268261 | P1 | |
ENST00000567942.1 | n.343T>C | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251246Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135834
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461350Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727016
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 29, 2024 | Variant summary: PMM2 c.653A>G (p.His218Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251246 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.653A>G in individuals affected with Congenital Disorder Of Glycosylation Type 1a and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at