19-51056645-C-G

Variant names:

• chr19-51056645-C-G
• rs141343299
• NM_015596.3:c.776G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015596.3(KLK13):​c.776G>C​(p.Arg259Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLK13 NM_015596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 0 publications found

Genes affected

KLK13 (HGNC:6361): (kallikrein related peptidase 13) 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. Expression of this gene is regulated by steroid hormones and may be useful as a marker for breast cancer. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31022134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015596.3. 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
	KLK13	NM_015596.3	MANE Select	c.776G>C	p.Arg259Pro	missense	Exon 5 of 5	NP_056411.1	Q9UKR3-1
	KLK13	NM_001348177.2		c.557G>C	p.Arg186Pro	missense	Exon 5 of 5	NP_001335106.1	Q86VI7
	KLK13	NM_001348178.2		c.320G>C	p.Arg107Pro	missense	Exon 3 of 3	NP_001335107.1	Q9UKR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK13	ENST00000595793.6	TSL:1 MANE Select	c.776G>C	p.Arg259Pro	missense	Exon 5 of 5	ENSP00000470555.1	Q9UKR3-1
	KLK13	ENST00000595547.5	TSL:1	c.557G>C	p.Arg186Pro	missense	Exon 5 of 5	ENSP00000470245.1	Q86VI7
	KLK13	ENST00000335422.3	TSL:1	c.320G>C	p.Arg107Pro	missense	Exon 3 of 3	ENSP00000334079.3	Q9UKR3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	5.4
DANN	Benign	0.91
DEOGEN2	Uncertain	0.64	D
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		-2.3
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		0.55	P
Vest4		0.22
MutPred		0.51		Loss of MoRF binding (P = 0.0209)
MVP		0.84
MPC		0.25
ClinPred		0.47	T
GERP RS		-8.3
Varity_R		0.84
gMVP		0.88
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs141343299; hg19: chr19-51559902;