chr19-50980448-G-C

Variant names:

• chr19-50980448-G-C
• rs143034119
• NM_005046.4:c.261C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005046.4(KLK7):​c.261C>G​(p.Asp87Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,908 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000099 (1 hom., cov: 29)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: KLK7 NM_005046.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.907
• Publications: 0 publications found

Genes affected

KLK7 (HGNC:6368): (kallikrein related peptidase 7) This gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis. The encoded protein may play a role in cancer invasion and metastasis, and increased expression of this gene is associated with unfavorable prognosis and progression of several types of cancer. Polymorphisms in this gene may play a role in the development of atopic dermatitis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is one of fifteen kallikrein subfamily members located in a gene cluster on chromosome 19. [provided by RefSeq, May 2011]

ENSG00000267879 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.07358813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005046.4. 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
	KLK7	NM_005046.4	MANE Select	c.261C>G	p.Asp87Glu	missense	Exon 4 of 6	NP_005037.1	P49862-1
	KLK7	NM_139277.2		c.261C>G	p.Asp87Glu	missense	Exon 4 of 6	NP_644806.1	P49862-1
	KLK7	NM_001243126.1		c.240C>G	p.Asp80Glu	missense	Exon 3 of 5	NP_001230055.1	P49862

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK7	ENST00000595820.6	TSL:1 MANE Select	c.261C>G	p.Asp87Glu	missense	Exon 4 of 6	ENSP00000470538.1	P49862-1
	KLK7	ENST00000597707.5	TSL:1	c.45C>G	p.Asp15Glu	missense	Exon 3 of 5	ENSP00000469950.1	P49862-2
	KLK7	ENST00000391807.5	TSL:5	c.261C>G	p.Asp87Glu	missense	Exon 4 of 6	ENSP00000375683.1	P49862-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152104 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.00

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: 0.000206

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000677 AC: 17 AN: 251220 AF XY: 0.0000663

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: 0.000150

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000752 AC: 110 AN: 1461804 Hom.: 0 Cov.: 33 AF XY: 0.0000825 AC XY: 60 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000944 AC: 105 AN: 1111956

Other (OTH) AF: 0.0000662 AC: 4 AN: 60388

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152104 Hom.: 1 Cov.: 29 AF XY: 0.0000942 AC XY: 7 AN XY: 74282

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000198 Hom.: 0

Bravo AF: 0.0000945

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.19
DANN	Benign	0.60
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0084	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-0.91
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.19
Sift	Benign	0.57	T
Sift4G	Benign	0.69	T
Polyphen		0.0080	B
Vest4		0.068
MutPred		0.24		Loss of sheet (P = 0.0817)
MVP		0.64
MPC		0.032
ClinPred		0.019	T
GERP RS		-3.5
Varity_R		0.12
gMVP		0.35
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: rs143034119; hg19: chr19-51483704;