rs766128169

Variant names:

• chr19-51006658-C-A
• rs766128169
• NM_012315.2:c.266G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51006658-C-A
• chr19-51006658-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012315.2(KLK9):​c.266G>T​(p.Arg89Leu) 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R89Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLK9 NM_012315.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

Genes affected

KLK9 (HGNC:6370): (kallikrein related peptidase 9) The protein encoded by this gene is a kallikrein-related serine protease. This gene is activated by steroid hormones in a human breast cancer cell line, making it a good marker for cancer detection. The encoded protein is found primarily in the cytoplasm.[provided by RefSeq, Oct 2010]

ENSG00000269741 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16233742).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK9	NM_012315.2	c.266G>T	p.Arg89Leu	missense_variant	Exon 3 of 5	ENST00000594211.2	NP_036447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK9	ENST00000594211.2	c.266G>T	p.Arg89Leu	missense_variant	Exon 3 of 5	1	NM_012315.2	ENSP00000469417.1
ENSG00000269741	ENST00000250366.6	n.266G>T		non_coding_transcript_exon_variant	Exon 3 of 7	2		ENSP00000250366.5
KLK9	ENST00000544410.1	n.109G>T		non_coding_transcript_exon_variant	Exon 2 of 4	2		ENSP00000443289.1
ENSG00000267879	ENST00000594512.1	n.430-5365C>A		intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.016	N
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.40	T
Sift4G	Benign	0.38	T
Polyphen		0.0020	B
Vest4		0.19
MutPred		0.36		Gain of catalytic residue at Q86 (P = 0.1287);
MVP		0.70
ClinPred		0.14	T
GERP RS		1.7
Varity_R		0.11
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766128169; hg19: chr19-51509914;