chr16-8801859-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_000303.3(PMM2):c.127G>C(p.Val43Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,612,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V43M) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000303.3 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 | UniProt |
---|---|---|---|---|---|---|---|
PMM2 | NM_000303.3 | c.127G>C | p.Val43Leu | missense_variant | 2/8 | ENST00000268261.9 | |
PMM2 | XM_047434215.1 | c.-46G>C | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMM2 | ENST00000268261.9 | c.127G>C | p.Val43Leu | missense_variant | 2/8 | 1 | NM_000303.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249760Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135030
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460224Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726362
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
ClinVar
Submissions by phenotype
PMM2-congenital disorder of glycosylation Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 14, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 04, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 43 of the PMM2 protein (p.Val43Leu). This variant is present in population databases (rs376754460, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1053724). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at