19-51016108-T-G

Variant names:

• chr19-51016108-T-G
• rs2075688
• NM_145888.3:c.318A>C

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.318A>C​(p.Gly106Gly) 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
• Publications: 18 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=-0.87).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	NM_145888.3	MANE Select	c.318A>C	p.Gly106Gly	synonymous	Exon 4 of 6	NP_665895.1
	KLK10	NM_001077500.2		c.318A>C	p.Gly106Gly	synonymous	Exon 4 of 6	NP_001070968.1
	KLK10	NM_002776.5		c.318A>C	p.Gly106Gly	synonymous	Exon 4 of 6	NP_002767.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	ENST00000358789.8	TSL:1 MANE Select	c.318A>C	p.Gly106Gly	synonymous	Exon 4 of 6	ENSP00000351640.2
	KLK10	ENST00000309958.7	TSL:1	c.318A>C	p.Gly106Gly	synonymous	Exon 4 of 6	ENSP00000311746.2
	KLK10	ENST00000601467.1	TSL:1	n.26A>C		non_coding_transcript_exon	Exon 3 of 5	ENSP00000472773.1

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

GnomAD2 exomes AF: 0.616 AC: 122393 AN: 198758 AF XY: 0.601

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 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

African (AFR) AF: 0.935 AC: 30398 AN: 32504

American (AMR) AF: 0.662 AC: 26199 AN: 39598

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 15539 AN: 25524

East Asian (EAS) AF: 0.619 AC: 23357 AN: 37746

South Asian (SAS) AF: 0.474 AC: 38790 AN: 81814

European-Finnish (FIN) AF: 0.599 AC: 30422 AN: 50800

Middle Eastern (MID) AF: 0.605 AC: 3457 AN: 5718

European-Non Finnish (NFE) AF: 0.629 AC: 688967 AN: 1095010

Other (OTH) AF: 0.642 AC: 37984 AN: 59178

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

African (AFR) AF: 0.924 AC: 38398 AN: 41554

American (AMR) AF: 0.691 AC: 10566 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2095 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3263 AN: 5158

South Asian (SAS) AF: 0.453 AC: 2188 AN: 4830

European-Finnish (FIN) AF: 0.594 AC: 6282 AN: 10584

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42420 AN: 67964

Other (OTH) AF: 0.682 AC: 1441 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.59
PhyloP100		-4.9
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2075688; hg19: chr19-51519364; COSMIC: COSV59397390; COSMIC: COSV59397390;