NM_001369775.2:c.176G>T

Variant names:

• chr19-51081568-C-A
• rs781139205
• NM_001369775.2:c.176G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369775.2(KLK14):​c.176G>T​(p.Gly59Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,544,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: KLK14 NM_001369775.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.101
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12064105).

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.176G>T	p.Gly59Val	missense	Exon 3 of 6	NP_001356704.1	A0A1R3UHJ7
	KLK14	NM_001311182.2		c.176G>T	p.Gly59Val	missense	Exon 4 of 8	NP_001298111.2	A0A1R3UHJ7
	KLK14	NM_022046.6		c.176G>T	p.Gly59Val	missense	Exon 4 of 7	NP_071329.3	A0A1R3UHJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK14	ENST00000650543.2	MANE Select	c.176G>T	p.Gly59Val	missense	Exon 3 of 6	ENSP00000497141.1	A0A1R3UHJ7
	KLK14	ENST00000156499.7	TSL:1	c.176G>T	p.Gly59Val	missense	Exon 4 of 8	ENSP00000156499.3	A0A1R3UHJ7
	KLK14	ENST00000391802.1	TSL:5	c.224G>T	p.Gly75Val	missense	Exon 4 of 7	ENSP00000375678.1	Q9P0G3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000204 AC: 3 AN: 146738 AF XY: 0.0000257

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000542

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000754 AC: 105 AN: 1392200 Hom.: 0 Cov.: 31 AF XY: 0.0000744 AC XY: 51 AN XY: 685900

African (AFR) AF: 0.00 AC: 0 AN: 31508

American (AMR) AF: 0.00 AC: 0 AN: 34884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24658

East Asian (EAS) AF: 0.00 AC: 0 AN: 35678

South Asian (SAS) AF: 0.00 AC: 0 AN: 78326

European-Finnish (FIN) AF: 0.0000204 AC: 1 AN: 49120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.0000958 AC: 103 AN: 1074768

Other (OTH) AF: 0.0000173 AC: 1 AN: 57642

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

African (AFR) AF: 0.0000241 AC: 1 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	7.3
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.66	N
PhyloP100		-0.10
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.33
Sift	Benign	0.036	D
Sift4G	Benign	0.16	T
Polyphen		0.62	P
Vest4		0.19
MutPred		0.49		Loss of glycosylation at S74 (P = 0.0694)
MVP		0.30
MPC		0.18
ClinPred		0.057	T
GERP RS		-1.1
Varity_R		0.071
gMVP		0.67
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs781139205; hg19: chr19-51584825;