chr20-32210191-A-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_015352.2(POFUT1):āc.245A>Cā(p.Asn82Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_015352.2 missense, splice_region
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POFUT1 | NM_015352.2 | c.245A>C | p.Asn82Thr | missense_variant, splice_region_variant | 2/7 | ENST00000375749.8 | NP_056167.1 | |
POFUT1 | NM_172236.2 | c.245A>C | p.Asn82Thr | missense_variant, splice_region_variant | 2/5 | NP_758436.1 | ||
POFUT1 | XM_047440079.1 | c.-79+2126A>C | intron_variant | XP_047296035.1 | ||||
POFUT1 | XR_007067447.1 | n.307A>C | splice_region_variant, non_coding_transcript_exon_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POFUT1 | ENST00000375749.8 | c.245A>C | p.Asn82Thr | missense_variant, splice_region_variant | 2/7 | 1 | NM_015352.2 | ENSP00000364902 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152026Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251458Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727228
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152026Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74230
ClinVar
Submissions by phenotype
Dowling-Degos disease 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 22, 2022 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with POFUT1-related conditions. This variant is present in population databases (rs745942782, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 82 of the POFUT1 protein (p.Asn82Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at