rs117229324

Variant names:

• chr19-51082721-C-A
• rs117229324
• NM_001369775.2:c.-23+1G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-51082721-C-A
• chr19-51082721-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001369775.2(KLK14):​c.-23+1G>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLK14 NM_001369775.2 splice_donor, intron
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 0 publications found

Genes affected

KLK14 (HGNC:6362): (kallikrein related peptidase 14) This gene encodes a member of the kallikrein subfamily of serine proteases that have diverse physiological functions such as regulation of blood pressure and desquamation. The altered expression of this gene is implicated in the progression of different cancers including breast and prostate tumors. The encoded protein is a precursor that is proteolytically processed to generate the functional enzyme. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369775.2. 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
	KLK14	NM_001369775.2	MANE Select	c.-23+1G>T		splice_donor intron	N/A	NP_001356704.1	A0A1R3UHJ7
	KLK14	NM_001311182.2		c.-23+1G>T		splice_donor intron	N/A	NP_001298111.2	A0A1R3UHJ7
	KLK14	NM_022046.6		c.-23+1G>T		splice_donor intron	N/A	NP_071329.3	A0A1R3UHJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	ENST00000650543.2	MANE Select	c.-23+1G>T		splice_donor intron	N/A	ENSP00000497141.1	A0A1R3UHJ7
	KLK14	ENST00000156499.7	TSL:1	c.-23+1G>T		splice_donor intron	N/A	ENSP00000156499.3	A0A1R3UHJ7
	KLK14	ENST00000391802.1	TSL:5	c.26+1G>T		splice_donor intron	N/A	ENSP00000375678.1	Q9P0G3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111980

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	18
DANN	Benign	0.75
Eigen	Benign	0.10
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.030	N
PhyloP100		-0.026
GERP RS		-0.95
PromoterAI		-0.073	Neutral
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.71
SpliceAI score (max)		0.84		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.84		Position offset: 1

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

Other links and lift over

dbSNP: rs117229324; hg19: chr19-51585978;