chr19-50907030-G-T

Variant names:

• chr19-50907030-G-T
• NM_004917.5:c.669C>A

Variant summary

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

The NM_004917.5(KLK4):​c.669C>A​(p.Phe223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/19 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: not found (cov: 32)
• Consequence: KLK4 NM_004917.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

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 rank	MANE	Protein	UniProt
KLK4	NM_004917.5	c.669C>A	p.Phe223Leu	missense_variant	Exon 6 of 6	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2	c.384C>A	p.Phe128Leu	missense_variant	Exon 5 of 5		NP_001289890.1
KLK4	NR_126566.2	n.658C>A		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK4	ENST00000324041.6	c.669C>A	p.Phe223Leu	missense_variant	Exon 6 of 6	1	NM_004917.5	ENSP00000326159.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	0.66
DANN	Benign	0.69
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.30	T
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.31
Sift	Benign	0.057	T
Sift4G	Uncertain	0.014	D
Vest4		0.10
MutPred		0.81		Loss of methylation at K225 (P = 0.1162);
MVP		0.57
MPC		0.40
ClinPred		0.066	T
GERP RS		-7.3
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr19-51410286;