ENST00000514141.5:n.*1298T>C

Variant names:

• chr5-75598084-T-C
• rs786205688
• ENST00000514141.5:n.*1298T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The ENST00000514141.5(POLK):​n.*1298T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 507,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: POLK ENST00000514141.5 non_coding_transcript_exon
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.884
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-75598084-T-C is Pathogenic according to our data. Variant chr5-75598084-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 190430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLK	NR_144315.3	n.2544T>C		non_coding_transcript_exon_variant	Exon 14 of 14
POLK	NR_170559.3	n.2533T>C		non_coding_transcript_exon_variant	Exon 14 of 14
POLK	NR_170560.3	n.2765T>C		non_coding_transcript_exon_variant	Exon 16 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLK	ENST00000241436.9	c.*66T>C		3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000241436.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000197 AC: 1 AN: 507340 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 267772

African (AFR) AF: 0.00 AC: 0 AN: 10508

American (AMR) AF: 0.00 AC: 0 AN: 13722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13226

East Asian (EAS) AF: 0.00 AC: 0 AN: 25556

South Asian (SAS) AF: 0.00 AC: 0 AN: 32484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2086

European-Non Finnish (NFE) AF: 0.00000292 AC: 1 AN: 341954

Other (OTH) AF: 0.00 AC: 0 AN: 26280

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Prostate cancer Pathogenic:1

Sep 24, 2013

Tulane Cancer Center, Tulane University

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.60
PhyloP100		0.88
Mutation Taster		=37/63	disease causing (ClinVar)

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: rs786205688; hg19: chr5-74893909;