19-51034426-C-T

Variant names:

• chr19-51034426-C-T
• rs3865443
• NM_001370125.1:c.37+159G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370126.1(KLK12):​c.-35G>A variant causes a splice region 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. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLK12 NM_001370126.1 splice_region
• Scores: Splicing: ADA: 0.00005159
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 9 publications found

Genes affected

KLK12 (HGNC:6360): (kallikrein related peptidase 12) 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. Alternate splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000268906 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370126.1. 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
	KLK12	NM_001370125.1	MANE Select	c.37+159G>A		intron	N/A	NP_001357054.1	Q9UKR0-1
	KLK12	NM_001370126.1		c.-35G>A		splice_region	Exon 2 of 6	NP_001357055.1	Q49AM7
	KLK12	NM_001370128.1		c.-35G>A		splice_region	Exon 2 of 5	NP_001357057.1	B9EGA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK12	ENST00000684732.1	MANE Select	c.37+159G>A		intron	N/A	ENSP00000508282.1	Q9UKR0-1
	KLK12	ENST00000525263.5	TSL:1	c.37+159G>A		intron	N/A	ENSP00000436458.1	Q9UKR0-1
	KLK12	ENST00000529888.5	TSL:1	c.37+159G>A		intron	N/A	ENSP00000434036.1	Q9UKR0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 22063

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_noAF	Benign	-0.91
CADD	Benign	19
DANN	Benign	0.27
PhyloP100		0.043
PromoterAI		0.035	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000052
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.52		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3865443; hg19: chr19-51537682;