Variant rs12366 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000483063.2(POLE4):c.50G>A(p.Gly17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000734 in 1,361,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G17V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

POLE4
ENST00000483063.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.995

Variant links:

Genes affected

POLE4 (HGNC:18755): (DNA polymerase epsilon 4, accessory subunit) POLE4 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]

POLE4 links:

LOC105374809 (HGNC:):

LOC105374809 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.070767015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
POLE4	NM_019896.4 linkuse as main transcript	c.50G>A	p.Gly17Glu	missense_variant	1/4	ENST00000483063.2	NP_063949.2
LOC105374809	XR_002959406.2 linkuse as main transcript	n.148+3C>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant
LOC105374809	XR_007087109.1 linkuse as main transcript	n.148+3C>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
POLE4	ENST00000483063.2 linkuse as main transcript	c.50G>A	p.Gly17Glu	missense_variant	1/4	1	NM_019896.4	ENSP00000420176	P1
POLE4	ENST00000459636.5 linkuse as main transcript	n.24G>A		non_coding_transcript_exon_variant	1/4	3
POLE4	ENST00000485527.5 linkuse as main transcript	n.25G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000876

AC:

AN:

114154

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

62528

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000231

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000734

AC:

AN:

1361626

Hom.:

Cov.:

AF XY:

0.00000596

AC XY:

AN XY:

671644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000846

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.00056

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.48

M_CAP

Benign

0.029

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

0.79

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.010

REVEL

Benign

0.069

Sift

Benign

0.30

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.13

MutPred

0.12

Loss of catalytic residue at G17 (P = 0.0746);

MVP

0.41

MPC

1.1

ClinPred

0.39

GERP RS

3.6

Varity_R

0.043

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over