8-42361331-CC-TT

Variant names:

• chr8-42361331-CC-TT
• NM_002690.3:c.587_588delCCinsTT
• POLB p.Thr196Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002690.3(POLB):​c.587_588delCCinsTT​(p.Thr196Ile) variant causes a missense change involving the alteration of a conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLB NM_002690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.69
• Publications: 0 publications found

Genes affected

POLB (HGNC:9174): (DNA polymerase beta) The protein encoded by this gene is a DNA polymerase involved in base excision and repair, also called gap-filling DNA synthesis. The encoded protein, acting as a monomer, is normally found in the cytoplasm, but it translocates to the nucleus upon DNA damage. Several transcript variants of this gene exist, but the full-length nature of only one has been described to date. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002690.3. 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
	POLB	NM_002690.3	MANE Select	c.587_588delCCinsTT	p.Thr196Ile	missense	N/A	NP_002681.1	P06746

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLB	ENST00000265421.9	TSL:1 MANE Select	c.587_588delCCinsTT	p.Thr196Ile	missense	N/A	ENSP00000265421.4	P06746
	POLB	ENST00000929417.1		c.587_588delCCinsTT	p.Thr196Ile	missense	N/A	ENSP00000599476.1
	POLB	ENST00000518925.5	TSL:5	c.692_693delCCinsTT	p.Thr231Ile	missense	N/A	ENSP00000430784.1	E7EW18

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

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: chr8-42218849;