Genetic Variant POLI:p.Asp20Gly (chr18-54269605-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007195.3(POLI):c.59A>G(p.Asp20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,501,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

POLI
NM_007195.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

Publications

1 publications found

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:

ENSG00000277324 (HGNC:):

ENSG00000277324 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06531498).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007195.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLI	NM_007195.3	MANE Select	c.59A>G	p.Asp20Gly	missense	Exon 1 of 10	NP_009126.2	Q9UNA4
POLI	NM_001351610.1		c.59A>G	p.Asp20Gly	missense	Exon 1 of 9	NP_001338539.1
POLI	NM_001351613.1		c.59A>G	p.Asp20Gly	missense	Exon 1 of 9	NP_001338542.1	J3KQ09

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POLI	ENST00000579534.6	TSL:1 MANE Select	c.59A>G	p.Asp20Gly	missense	Exon 1 of 10	ENSP00000462664.1	Q9UNA4
POLI	ENST00000579434.5	TSL:1	c.-496A>G		5_prime_UTR	Exon 1 of 9	ENSP00000462681.1	J3KSW2
POLI	ENST00000930897.1		c.59A>G	p.Asp20Gly	missense	Exon 1 of 9	ENSP00000600956.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000388

AC:

AN:

103010

AF XY:

0.0000527

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:

0.0000242

Gnomad OTH exome

AF:

0.000352

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1349812

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

665954

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26624

American (AMR)

AF:

0.00

AC:

AN:

25594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23306

East Asian (EAS)

AF:

0.00

AC:

AN:

30474

South Asian (SAS)

AF:

0.0000400

AC:

AN:

75018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46102

Middle Eastern (MID)

AF:

0.000997

AC:

AN:

5014

European-Non Finnish (NFE)

AF:

0.0000141

AC:

AN:

1061844

Other (OTH)

AF:

0.0000537

AC:

AN:

55836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000454

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000192

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.10

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.45

M_CAP

Benign

0.060

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

PhyloP100

0.85

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.094

Sift

Benign

0.47

Sift4G

Uncertain

0.055

Polyphen

0.020

Vest4

0.14

MutPred

0.24

Gain of helix (P = 0.0696)

MVP

0.35

MPC

0.013

ClinPred

0.050

GERP RS

0.058

PromoterAI

-0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over