rs2075696

Variant names:

• chr19-51014966-G-A
• rs2075696
• NM_145888.3:c.679-14C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145888.3(KLK10):​c.679-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,607,592 control chromosomes in the GnomAD database, including 96,090 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 0.38 (11517 hom., cov: 31)
  • Exomes 𝑓: 0.34 (84573 hom.)
• Consequence: KLK10 NM_145888.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 10 publications found

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]

ENSG00000268739 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK10	NM_145888.3	c.679-14C>T		intron_variant	Intron 5 of 5	ENST00000358789.8	NP_665895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8	c.679-14C>T		intron_variant	Intron 5 of 5	1	NM_145888.3	ENSP00000351640.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57475 AN: 151734 Hom.: 11504 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.344 AC: 84927 AN: 247178 AF XY: 0.333

Gnomad AFR exome AF: 0.501

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.278

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.337 AC: 490013 AN: 1455740 Hom.: 84573 Cov.: 33 AF XY: 0.333 AC XY: 240863 AN XY: 724246

African (AFR) AF: 0.504 AC: 16804 AN: 33310

American (AMR) AF: 0.471 AC: 20700 AN: 43970

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 7018 AN: 25912

East Asian (EAS) AF: 0.250 AC: 9897 AN: 39648

South Asian (SAS) AF: 0.250 AC: 21473 AN: 85868

European-Finnish (FIN) AF: 0.277 AC: 14688 AN: 53072

Middle Eastern (MID) AF: 0.319 AC: 1667 AN: 5224

European-Non Finnish (NFE) AF: 0.341 AC: 377668 AN: 1108678

Other (OTH) AF: 0.335 AC: 20098 AN: 60058

GnomAD4 genome AF: 0.379 AC: 57527 AN: 151852 Hom.: 11517 Cov.: 31 AF XY: 0.373 AC XY: 27677 AN XY: 74218

African (AFR) AF: 0.502 AC: 20760 AN: 41352

American (AMR) AF: 0.431 AC: 6583 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.258 AC: 1327 AN: 5152

South Asian (SAS) AF: 0.233 AC: 1117 AN: 4802

European-Finnish (FIN) AF: 0.263 AC: 2780 AN: 10562

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22812 AN: 67932

Other (OTH) AF: 0.363 AC: 765 AN: 2106

Alfa AF: 0.349 Hom.: 3744

Bravo AF: 0.401

Asia WGS AF: 0.222 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.3
DANN	Benign	0.70
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075696; hg19: chr19-51518222; COSMIC: COSV59398843; COSMIC: COSV59398843;