12-52447230-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_005555.4(KRT6B):āc.1655C>Gā(p.Thr552Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,006 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005555.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251444Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135892
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461746Hom.: 1 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727190
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 552 of the KRT6B protein (p.Thr552Ser). This variant is present in population databases (rs775142460, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with KRT6B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KRT6B protein function with a negative predictive value of 95%. 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