chr19-51014939-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_145888.3(KLK10):c.692G>A(p.Gly231Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,218 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G231S) has been classified as Uncertain significance.
Frequency
Consequence
NM_145888.3 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 |
---|---|---|---|---|---|---|---|
KLK10 | NM_145888.3 | c.692G>A | p.Gly231Asp | missense_variant | 6/6 | ENST00000358789.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLK10 | ENST00000358789.8 | c.692G>A | p.Gly231Asp | missense_variant | 6/6 | 1 | NM_145888.3 | P1 | |
KLK10 | ENST00000309958.7 | c.692G>A | p.Gly231Asp | missense_variant | 6/6 | 1 | P1 | ||
KLK10 | ENST00000601467.1 | c.*268G>A | 3_prime_UTR_variant, NMD_transcript_variant | 5/5 | 1 | ||||
KLK10 | ENST00000391805.5 | c.692G>A | p.Gly231Asp | missense_variant | 6/6 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152030Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250652Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135476
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461188Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726898
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152030Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74248
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2023 | The c.692G>A (p.G231D) alteration is located in exon 6 (coding exon 5) of the KLK10 gene. This alteration results from a G to A substitution at nucleotide position 692, causing the glycine (G) at amino acid position 231 to be replaced by an aspartic acid (D). 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