Genetic Variant POLE3:p.Arg34Arg (chr9-113410107-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017443.5(POLE3):c.100C>A(p.Arg34Arg) variant causes a synonymous change. 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POLE3
NM_017443.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

Publications

0 publications found

Variant links:

Genes affected

POLE3 (HGNC:13546): (DNA polymerase epsilon 3, accessory subunit) POLE3 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]

POLE3 links:

C9orf43 (HGNC:23570): (chromosome 9 open reading frame 43)

C9orf43 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLE3	NM_017443.5 link	c.100C>A	p.Arg34Arg	synonymous_variant	Exon 3 of 5	ENST00000374171.5	NP_059139.3	Q9NRF9A0A024R829
POLE3	NM_001278255.1 link	c.100C>A	p.Arg34Arg	synonymous_variant	Exon 3 of 5		NP_001265184.1	Q9NRF9A0A024R829
POLE3	NM_001433719.1 link	c.100C>A	p.Arg34Arg	synonymous_variant	Exon 2 of 4		NP_001420648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLE3	ENST00000374171.5 link	c.100C>A	p.Arg34Arg	synonymous_variant	Exon 3 of 5	2	NM_017443.5	ENSP00000363286.4		Q9NRF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000475

AC:

AN:

210446

AF XY:

0.00000883

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1437704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712978

African (AFR)

AF:

0.00

AC:

AN:

33208

American (AMR)

AF:

0.00

AC:

AN:

40654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25592

East Asian (EAS)

AF:

0.00

AC:

AN:

38850

South Asian (SAS)

AF:

0.00

AC:

AN:

82962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4882

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100908

Other (OTH)

AF:

0.00

AC:

AN:

59416

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.7

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over