19-51016108-T-G

Position:

• chr19-51016108-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145888.3(KLK10):​c.318A>C​(p.Gly106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,580,068 control chromosomes in the GnomAD database, including 323,089 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 0.71 (39425 hom., cov: 33)
  • Exomes 𝑓: 0.63 (283664 hom.)
• Consequence: KLK10 NM_145888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.93

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-4.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK10	NM_145888.3	c.318A>C	p.Gly106=	synonymous_variant	4/6	ENST00000358789.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK10	ENST00000358789.8	c.318A>C	p.Gly106=	synonymous_variant	4/6	1	NM_145888.3	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107266 AN: 152056 Hom.: 39377 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.685

GnomAD3 exomes AF: 0.616 AC: 122393 AN: 198758 Hom.: 38580 AF XY: 0.601 AC XY: 64169 AN XY: 106740

Gnomad AFR exome AF: 0.923

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.604

Gnomad EAS exome AF: 0.634

Gnomad SAS exome AF: 0.463

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.620

GnomAD4 exome AF: 0.627 AC: 895113 AN: 1427892 Hom.: 283664 Cov.: 48 AF XY: 0.621 AC XY: 438943 AN XY: 707234

Gnomad4 AFR exome AF: 0.935

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.706 AC: 107377 AN: 152176 Hom.: 39425 Cov.: 33 AF XY: 0.700 AC XY: 52043 AN XY: 74386

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.682

Alfa AF: 0.664 Hom.: 14203

Bravo AF: 0.727

Asia WGS AF: 0.549 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2075688; hg19: chr19-51519364; COSMIC: COSV59397390; COSMIC: COSV59397390;