rs200569857

Variant names:

• chr19-51056672-C-G
• NM_015596.3:c.749G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-51056672-C-G
• chr19-51056672-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015596.3(KLK13):​c.749G>C​(p.Arg250Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R250H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KLK13 NM_015596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK13	NM_015596.3	c.749G>C	p.Arg250Pro	missense_variant	Exon 5 of 5	ENST00000595793.6	NP_056411.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK13	ENST00000595793.6	c.749G>C	p.Arg250Pro	missense_variant	Exon 5 of 5	1	NM_015596.3	ENSP00000470555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	D;D;.
Eigen	Benign	0.031
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.93	D;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	.;.;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	.;.;D
Sift4G	Benign	0.071	T;D;D
Polyphen		0.99	D;P;.
Vest4		0.67
MutPred		0.80		Loss of MoRF binding (P = 0.0082);.;.;
MVP		0.93
MPC		0.61
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.93
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-51559929;