chr19-50908611-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_004917.5(KLK4):c.443G>A(p.Cys148Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000613 in 1,614,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 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. C148F) has been classified as Uncertain significance.
Frequency
Consequence
NM_004917.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLK4 | NM_004917.5 | c.443G>A | p.Cys148Tyr | missense_variant | 4/6 | ENST00000324041.6 | |
KLK4 | NM_001302961.2 | c.158G>A | p.Cys53Tyr | missense_variant | 3/5 | ||
KLK4 | XM_011527545.4 | c.443G>A | p.Cys148Tyr | missense_variant | 3/4 | ||
KLK4 | NR_126566.2 | n.436G>A | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLK4 | ENST00000324041.6 | c.443G>A | p.Cys148Tyr | missense_variant | 4/6 | 1 | NM_004917.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152216Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251436Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135906
GnomAD4 exome AF: 0.0000602 AC: 88AN: 1461894Hom.: 1 Cov.: 32 AF XY: 0.0000660 AC XY: 48AN XY: 727248
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152216Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.443G>A (p.C148Y) alteration is located in exon 3 (coding exon 3) of the KLK4 gene. This alteration results from a G to A substitution at nucleotide position 443, causing the cysteine (C) at amino acid position 148 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at