8-42355555-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002690.3(POLB):​c.410G>T​(p.Arg137Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,439,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

POLB
NM_002690.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.17
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39754018).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POLBNM_002690.3 linkc.410G>T p.Arg137Leu missense_variant Exon 7 of 14 ENST00000265421.9 NP_002681.1 P06746

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POLBENST00000265421.9 linkc.410G>T p.Arg137Leu missense_variant Exon 7 of 14 1 NM_002690.3 ENSP00000265421.4 P06746

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1439192
Hom.:
0
Cov.:
24
AF XY:
0.00000139
AC XY:
1
AN XY:
717542
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.16e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.40
.;T;T
Eigen
Benign
0.034
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.83
.;L;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-3.3
D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0040
D;T;T
Sift4G
Benign
0.15
T;T;T
Polyphen
0.0010
.;B;.
Vest4
0.60
MutPred
0.64
.;Loss of MoRF binding (P = 0.0076);.;
MVP
0.46
MPC
0.81
ClinPred
0.94
D
GERP RS
5.3
Varity_R
0.56
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr8-42213073; API