rs193920890

Positions:

• chr1-152760413-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001025231.3(KPRP):​c.825T>A​(p.Phe275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KPRP NM_001025231.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.575

Genes affected

KPRP (HGNC:31823): (keratinocyte proline rich protein) This gene encodes a proline-rich skin protein possibly involved in keratinocyte differentiation. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036412388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KPRP	NM_001025231.3	c.825T>A	p.Phe275Leu	missense_variant	2/2	ENST00000606109.2	NP_001020402.1
KPRP	XM_047421164.1	c.825T>A	p.Phe275Leu	missense_variant	3/3		XP_047277120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KPRP	ENST00000606109.2	c.825T>A	p.Phe275Leu	missense_variant	2/2		NM_001025231.3	ENSP00000475216	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.026
DANN	Benign	0.79
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.41	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.64	T
Polyphen		0.027	B
Vest4		0.086
MutPred		0.096		Gain of catalytic residue at F275 (P = 0.1693);
MVP		0.13
ClinPred		0.055	T
GERP RS		-3.5
Varity_R		0.033
gMVP		0.076

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

Publications

LitVar

Other links and lift over

dbSNP: rs193920890; hg19: chr1-152732889; COSMIC: COSV64222889;