chr19-50980434-C-A

Variant names:

• chr19-50980434-C-A
• rs765835597
• NM_005046.4:c.275G>T

Variant summary

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

The NM_005046.4(KLK7):​c.275G>T​(p.Arg92Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KLK7 NM_005046.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01

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

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=0.25585854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK7	NM_005046.4	c.275G>T	p.Arg92Met	missense_variant	Exon 4 of 6	ENST00000595820.6	NP_005037.1
KLK7	NM_139277.2	c.275G>T	p.Arg92Met	missense_variant	Exon 4 of 6		NP_644806.1
KLK7	NM_001243126.1	c.254G>T	p.Arg85Met	missense_variant	Exon 3 of 5		NP_001230055.1
KLK7	NM_001207053.2	c.59G>T	p.Arg20Met	missense_variant	Exon 3 of 5		NP_001193982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK7	ENST00000595820.6	c.275G>T	p.Arg92Met	missense_variant	Exon 4 of 6	1	NM_005046.4	ENSP00000470538.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461826 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	5.3
DANN	Benign	0.71
DEOGEN2	Benign	0.29	T;T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.51	T;.;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.0	L;L;.;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.52	N;.;.;.
REVEL	Uncertain	0.31
Sift	Benign	0.14	T;.;.;.
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0030	B;B;.;.
Vest4		0.27
MutPred		0.73		Loss of MoRF binding (P = 0.0466);Loss of MoRF binding (P = 0.0466);.;.;
MVP		0.72
MPC		0.10
ClinPred		0.090	T
GERP RS		-5.3
Varity_R		0.17
gMVP		0.57

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: rs765835597; hg19: chr19-51483690; COSMIC: COSV100304391; COSMIC: COSV100304391;