rs3745535

Variant names:

• chr19-51017231-A-C
• rs3745535
• NM_145888.3:c.148T>G
• KLK10 p.Ser50Ala

Your query was ambiguous. Multiple possible variants found:

• chr19-51017231-A-C
• chr19-51017231-A-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.148T>G​(p.Ser50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,611,012 control chromosomes in the GnomAD database, including 341,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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 (40184 hom., cov: 34)
  • Exomes 𝑓: 0.64 (301282 hom.)
• Consequence: KLK10 NM_145888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 40 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.035569E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	NM_145888.3	MANE Select	c.148T>G	p.Ser50Ala	missense	Exon 3 of 6	NP_665895.1	O43240
	KLK10	NM_001077500.2		c.148T>G	p.Ser50Ala	missense	Exon 3 of 6	NP_001070968.1	O43240
	KLK10	NM_002776.5		c.148T>G	p.Ser50Ala	missense	Exon 3 of 6	NP_002767.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK10	ENST00000358789.8	TSL:1 MANE Select	c.148T>G	p.Ser50Ala	missense	Exon 3 of 6	ENSP00000351640.2	O43240
	KLK10	ENST00000309958.7	TSL:1	c.148T>G	p.Ser50Ala	missense	Exon 3 of 6	ENSP00000311746.2	O43240
	KLK10	ENST00000601467.1	TSL:1	n.-145T>G		non_coding_transcript_exon	Exon 2 of 5	ENSP00000472773.1	M0R2S4

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108456 AN: 152054 Hom.: 40134 Cov.: 34

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.687

GnomAD2 exomes AF: 0.637 AC: 153267 AN: 240468 AF XY: 0.624

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.666

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.651

Gnomad FIN exome AF: 0.622

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.639 AC: 932836 AN: 1458840 Hom.: 301282 Cov.: 57 AF XY: 0.633 AC XY: 459473 AN XY: 725610

African (AFR) AF: 0.937 AC: 31345 AN: 33444

American (AMR) AF: 0.668 AC: 29597 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 15965 AN: 26054

East Asian (EAS) AF: 0.629 AC: 24931 AN: 39614

South Asian (SAS) AF: 0.483 AC: 41584 AN: 86042

European-Finnish (FIN) AF: 0.619 AC: 32751 AN: 52878

Middle Eastern (MID) AF: 0.621 AC: 3377 AN: 5434

European-Non Finnish (NFE) AF: 0.643 AC: 714094 AN: 1110884

Other (OTH) AF: 0.651 AC: 39192 AN: 60170

GnomAD4 genome AF: 0.713 AC: 108569 AN: 152172 Hom.: 40184 Cov.: 34 AF XY: 0.707 AC XY: 52623 AN XY: 74390

African (AFR) AF: 0.926 AC: 38505 AN: 41570

American (AMR) AF: 0.693 AC: 10597 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2099 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3291 AN: 5152

South Asian (SAS) AF: 0.460 AC: 2214 AN: 4818

European-Finnish (FIN) AF: 0.614 AC: 6494 AN: 10574

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43201 AN: 67990

Other (OTH) AF: 0.683 AC: 1442 AN: 2110

Alfa AF: 0.657 Hom.: 145499

Bravo AF: 0.732

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	3.4
DANN	Benign	0.56
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.045	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.70	N
PhyloP100		-2.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.16
Sift	Benign	0.93	T
Sift4G	Benign	0.84	T
Varity_R		0.14
gMVP		0.23
Mutation Taster		=99/1	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3745535;

hg19: chr19-51520487;

COSMIC: COSV59397518;

COSMIC: COSV59397518;