Genetic Variant POLI:p.Ile70Val (chr18-54271452-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_007195.3(POLI):c.208A>G(p.Ile70Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000914 in 1,608,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

POLI
NM_007195.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

POLI (HGNC:9182): (DNA polymerase iota) The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion. [provided by RefSeq, May 2017]

POLI links:

Genome browser will be placed here

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=0.22674048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLI	NM_007195.3 link	c.208A>G	p.Ile70Val	missense_variant	Exon 2 of 10	ENST00000579534.6	NP_009126.2	Q9UNA4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6 link	c.208A>G	p.Ile70Val	missense_variant	Exon 2 of 10	1	NM_007195.3	ENSP00000462664.1		Q9UNA4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000808

AC:

AN:

247434

Hom.:

AF XY:

0.0000748

AC XY:

AN XY:

133668

show subpopulations

Gnomad AFR exome

AF:

0.0000624

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:

0.0000464

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000961

AC:

140

AN:

1456590

Hom.:

Cov.:

AF XY:

0.0000952

AC XY:

AN XY:

724712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 18, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.208A>G (p.I70V) alteration is located in exon 2 (coding exon 2) of the POLI gene. This alteration results from a A to G substitution at nucleotide position 208, causing the isoleucine (I) at amino acid position 70 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

T;T;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.68

N;.;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.44

.;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.29

.;T;.;.

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.85

P;.;.;.

Vest4

0.35

MVP

0.55

MPC

0.033

ClinPred

0.17

GERP RS

5.1

Varity_R

0.18

gMVP

0.16

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over