rs1061368

Variant names:

• chr19-51016090-G-C
• rs1061368
• NM_145888.3:c.336C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145888.3(KLK10):​c.336C>G​(p.Thr112Thr) 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 NM_145888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 21 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KLK10	NM_145888.3	c.336C>G	p.Thr112Thr	synonymous_variant	Exon 4 of 6	ENST00000358789.8	NP_665895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK10	ENST00000358789.8	c.336C>G	p.Thr112Thr	synonymous_variant	Exon 4 of 6	1	NM_145888.3	ENSP00000351640.2

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

GnomAD2 exomes AF: 0.321 AC: 61478 AN: 191352 AF XY: 0.311

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 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

African (AFR) AF: 0.430 AC: 13912 AN: 32346

American (AMR) AF: 0.453 AC: 17527 AN: 38684

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 6978 AN: 25480

East Asian (EAS) AF: 0.241 AC: 9024 AN: 37510

South Asian (SAS) AF: 0.247 AC: 20062 AN: 81374

European-Finnish (FIN) AF: 0.278 AC: 14133 AN: 50758

Middle Eastern (MID) AF: 0.309 AC: 1767 AN: 5722

European-Non Finnish (NFE) AF: 0.340 AC: 371706 AN: 1092628

Other (OTH) AF: 0.328 AC: 19338 AN: 59006

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

African (AFR) AF: 0.427 AC: 17730 AN: 41526

American (AMR) AF: 0.422 AC: 6447 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1311 AN: 5162

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4832

European-Finnish (FIN) AF: 0.269 AC: 2853 AN: 10598

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22891 AN: 67994

Other (OTH) AF: 0.344 AC: 727 AN: 2112

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
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.28
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1061368; hg19: chr19-51519346; COSMIC: COSV59397980; COSMIC: COSV59397980;