rs3745535

chr19-51017231-A-Cchr19-51017231-A-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK10	NM_145888.3	c.148T>G	p.Ser50Ala	missense_variant	3/6	ENST00000358789.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK10	ENST00000358789.8	c.148T>G	p.Ser50Ala	missense_variant	3/6	1	NM_145888.3	P1

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

GnomAD3 exomes AF: 0.637 AC: 153267 AN: 240468 Hom.: 49863 AF XY: 0.624 AC XY: 81840 AN XY: 131190

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 SAS exome AF: 0.477

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

Gnomad4 AFR exome AF: 0.937

Gnomad4 AMR exome AF: 0.668

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.629

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.619

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.651

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

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.639

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.683

Alfa AF: 0.641 Hom.: 64425

Bravo AF: 0.732

TwinsUK AF: 0.644 AC: 2389

ALSPAC AF: 0.640 AC: 2468

ESP6500AA AF: 0.922 AC: 4053

ESP6500EA AF: 0.641 AC: 5503

ExAC AF: 0.636 AC: 76824

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0080	N
MetaRNN	Benign	0.0000010	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.70	N;N;N;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.37	N;N;N;.
REVEL	Benign	0.16
Sift	Benign	0.93	T;T;T;.
Sift4G	Benign	0.84	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.021
MPC		0.14
ClinPred		0.0012	T
GERP RS		-2.8
Varity_R		0.14
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs3745535; hg19: chr19-51520487; COSMIC: COSV59397518; COSMIC: COSV59397518;