19-51016095-G-A

Position:

• chr19-51016095-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145888.3(KLK10):​c.331C>T​(p.Arg111Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,578,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: KLK10 NM_145888.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK10	NM_145888.3	c.331C>T	p.Arg111Trp	missense_variant	4/6	ENST00000358789.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK10	ENST00000358789.8	c.331C>T	p.Arg111Trp	missense_variant	4/6	1	NM_145888.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152228 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000231 AC: 33 AN: 1426676 Hom.: 0 Cov.: 51 AF XY: 0.0000297 AC XY: 21 AN XY: 706596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000254

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000238

Gnomad4 OTH exome AF: 0.000102

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152228 Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.0000582 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000249 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.69	D;D;D;.
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.0071	N
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.2	M;M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.1	D;D;D;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.011	D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		1.0	D;D;D;.
Vest4		0.40
MVP		0.98
MPC		0.28
ClinPred		0.90	D
GERP RS		-2.3
Varity_R		0.48
gMVP		0.55

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: rs372547311; hg19: chr19-51519351;