NM_012427.5:c.664_665delCCinsTT

Variant names:

• chr19-50948701-GG-AA
• NM_012427.5:c.664_665delCCinsTT
• KLK5 p.Pro222Leu

Variant summary

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

The NM_012427.5(KLK5):​c.664_665delCCinsTT​(p.Pro222Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P222S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLK5 NM_012427.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.86
• Publications: 0 publications found

Genes affected

KLK5 (HGNC:6366): (kallikrein related peptidase 5) 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. Its expression is up-regulated by estrogens and progestins. The encoded protein is secreted and may be involved in desquamation in the epidermis. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012427.5. 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
	KLK5	NM_012427.5	MANE Select	c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	NP_036559.1	Q9Y337
	KLK5	NM_001077491.2		c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	NP_001070959.1	Q9Y337
	KLK5	NM_001077492.2		c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	NP_001070960.1	Q9Y337

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK5	ENST00000336334.8	TSL:1 MANE Select	c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	ENSP00000337733.2	Q9Y337
	KLK5	ENST00000391809.6	TSL:1	c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	ENSP00000375685.1	Q9Y337
	KLK5	ENST00000593428.5	TSL:1	c.664_665delCCinsTT	p.Pro222Leu	missense	N/A	ENSP00000471966.1	Q9Y337

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-51451957;