22-30610970-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000355.4(TCN2):c.164A>G(p.Tyr55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000355.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251488Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135922
GnomAD4 exome AF: 0.0000547 AC: 80AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000646 AC XY: 47AN XY: 727244
GnomAD4 genome AF: 0.0000986 AC: 15AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74314
ClinVar
Submissions by phenotype
Transcobalamin II deficiency Uncertain:1
This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 55 of the TCN2 protein (p.Tyr55Cys). This variant is present in population databases (rs201701227, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 573502). 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. 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