17-41610924-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_005557.4(KRT16):c.989G>A(p.Arg330His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R330L) has been classified as Benign.
Frequency
Consequence
NM_005557.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT16 | NM_005557.4 | c.989G>A | p.Arg330His | missense_variant | 5/8 | ENST00000301653.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT16 | ENST00000301653.9 | c.989G>A | p.Arg330His | missense_variant | 5/8 | 1 | NM_005557.4 | P1 | |
KRT16 | ENST00000593067.1 | c.275G>A | p.Arg92His | missense_variant | 6/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251474Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135918
GnomAD4 exome AF: 0.0000985 AC: 144AN: 1461876Hom.: 0 Cov.: 34 AF XY: 0.0000963 AC XY: 70AN XY: 727234
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74364
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 02, 2017 | The R330H variant in the KRT16 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R330H variant is observed in 2/66644 (0.003%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The R330H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R330H as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at