5-75596885-T-C

Variant names:

• chr5-75596885-T-C
• ENST00000241436.9:c.2192T>C

Variant summary

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

The NM_001387111.3(POLK):​c.2234T>C​(p.Leu745Pro) 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. 13/21 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: 32)
• Consequence: POLK NM_001387111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

Genes affected

POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

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=0.19417855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NM_001387111.3	c.2234T>C	p.Leu745Pro	missense_variant	Exon 14 of 16		NP_001374040.1
POLK	NM_001395894.1	c.2234T>C	p.Leu745Pro	missense_variant	Exon 15 of 17		NP_001382823.1
POLK	NM_001395897.1	c.2231T>C	p.Leu744Pro	missense_variant	Exon 14 of 16		NP_001382826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.2192T>C	p.Leu731Pro	missense_variant	Exon 13 of 15	1		ENSP00000241436.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.15
Sift	Benign	0.15	T;D
Sift4G	Benign	0.32	T;T
Polyphen		0.97	D;D
Vest4		0.27
MutPred		0.20		Gain of glycosylation at L731 (P = 0.0131);.;
MVP		0.71
MPC		0.37
ClinPred		0.63	D
GERP RS		3.1
Varity_R		0.14
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-74892710;