2-55636286-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033109.5(PNPT1):c.2303G>T(p.Ser768Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_033109.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PNPT1 | NM_033109.5 | c.2303G>T | p.Ser768Ile | missense_variant | Exon 28 of 28 | ENST00000447944.7 | NP_149100.2 | |
PNPT1 | XM_005264629.3 | c.2063G>T | p.Ser688Ile | missense_variant | Exon 28 of 28 | XP_005264686.1 | ||
PNPT1 | XM_017005172.2 | c.2063G>T | p.Ser688Ile | missense_variant | Exon 27 of 27 | XP_016860661.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152044Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251098Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135800
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461436Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727070
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. This variant is present in population databases (rs566113211, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 768 of the PNPT1 protein (p.Ser768Ile). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at