POLB p.Thr196Ser

Variant names:

• chr8-42361330-A-T
• NM_002690.3:c.586A>T
• POLB p.Thr196Ser

Your query was ambiguous. Multiple possible variants found:

• chr8-42361330-A-T
• chr8-42361331-C-G
• chr8-42361330-ACC-TCT
• chr8-42361330-ACC-TCA
• chr8-42361330-ACC-TCG
• chr8-42361331-CC-GT

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002690.3(POLB):​c.586A>T​(p.Thr196Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: POLB NM_002690.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.06
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30319542).

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.586A>T	p.Thr196Ser	missense	Exon 10 of 14	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.586A>T	p.Thr196Ser	missense	Exon 10 of 14	ENSP00000265421.4	P06746
	POLB	ENST00000929417.1		c.586A>T	p.Thr196Ser	missense	Exon 10 of 14	ENSP00000599476.1
	POLB	ENST00000518925.5	TSL:5	c.691A>T	p.Thr231Ser	missense	Exon 11 of 13	ENSP00000430784.1	E7EW18

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.82
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.0012
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
PromoterAI		0.0036	Neutral
Varity_R		0.52
gMVP		0.64
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr8-42218848;