rs2075689

chr19-51016003-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_145888.3(KLK10):c.423G>A(p.Leu141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,567,774 control chromosomes in the GnomAD database, including 242,802 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27676 hom., cov: 34)
  • Exomes 𝑓: 0.55 (215126 hom.)
• Consequence: KLK10 NM_145888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

Genes affected

KLK10 (HGNC:6358): (kallikrein related peptidase 10) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its encoded protein is secreted and may play a role in suppression of tumorigenesis in breast and prostate cancers. Alternate splicing of this gene results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.355 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK10	NM_145888.3	c.423G>A	p.Leu141=	synonymous_variant	4/6	ENST00000358789.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK10	ENST00000358789.8	c.423G>A	p.Leu141=	synonymous_variant	4/6	1	NM_145888.3	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90633 AN: 152074 Hom.: 27666 Cov.: 34

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.573

GnomAD3 exomes AF: 0.543 AC: 96443 AN: 177642 Hom.: 26628 AF XY: 0.529 AC XY: 50015 AN XY: 94592

Gnomad AFR exome AF: 0.719

Gnomad AMR exome AF: 0.613

Gnomad ASJ exome AF: 0.519

Gnomad EAS exome AF: 0.544

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.545

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.548 AC: 776232 AN: 1415582 Hom.: 215126 Cov.: 60 AF XY: 0.542 AC XY: 379357 AN XY: 699812

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.596 AC: 90682 AN: 152192 Hom.: 27676 Cov.: 34 AF XY: 0.593 AC XY: 44111 AN XY: 74394

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.569

Alfa AF: 0.563 Hom.: 26892

Bravo AF: 0.612

Asia WGS AF: 0.436 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	9.7
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2075689; hg19: chr19-51519259; COSMIC: COSV59398849; COSMIC: COSV59398849;