chr10-23192702-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_178161.3(PTF1A):c.172C>T(p.His58Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,579,648 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_178161.3 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTF1A | NM_178161.3 | c.172C>T | p.His58Tyr | missense_variant | 1/2 | ENST00000376504.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTF1A | ENST00000376504.4 | c.172C>T | p.His58Tyr | missense_variant | 1/2 | 1 | NM_178161.3 | P1 | |
PTF1A | ENST00000638469.1 | c.114+25C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152004Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000237 AC: 5AN: 210758Hom.: 0 AF XY: 0.0000172 AC XY: 2AN XY: 116362
GnomAD4 exome AF: 0.0000147 AC: 21AN: 1427534Hom.: 1 Cov.: 33 AF XY: 0.0000169 AC XY: 12AN XY: 710164
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 03, 2021 | This variant is present in population databases (rs759962056, ExAC 0.02%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PTF1A-related conditions. This sequence change replaces histidine with tyrosine at codon 58 of the PTF1A protein (p.His58Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at