rs1061368

Positions:

• chr19-51016090-G-C
• chr19-51016090-G-T

Variant summary

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

The ENST00000358789.8(KLK10):​c.336C>G​(p.Thr112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,575,702 control chromosomes in the GnomAD database, including 90,498 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 0.36 (10066 hom., cov: 34)
  • Exomes 𝑓: 0.33 (80432 hom.)
• Consequence: KLK10 ENST00000358789.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.451 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLK10	NM_145888.3	c.336C>G	p.Thr112=	synonymous_variant	4/6	ENST00000358789.8	NP_665895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8	c.336C>G	p.Thr112=	synonymous_variant	4/6	1	NM_145888.3	ENSP00000351640	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54448 AN: 152076 Hom.: 10059 Cov.: 34

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.321 AC: 61478 AN: 191352 Hom.: 10351 AF XY: 0.311 AC XY: 31889 AN XY: 102598

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.240

Gnomad FIN exome AF: 0.266

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.333 AC: 474447 AN: 1423508 Hom.: 80432 Cov.: 53 AF XY: 0.329 AC XY: 232167 AN XY: 704760

Gnomad4 AFR exome AF: 0.430

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.358 AC: 54478 AN: 152194 Hom.: 10066 Cov.: 34 AF XY: 0.353 AC XY: 26239 AN XY: 74402

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.344

Alfa AF: 0.335 Hom.: 2646

Bravo AF: 0.376

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1061368; hg19: chr19-51519346; COSMIC: COSV59397980; COSMIC: COSV59397980;