Variant 10-101580302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001174084.2(POLL):c.1309G>A(p.Gly437Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,742 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: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

POLL
NM_001174084.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52

Variant links:

Genes affected

POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]

POLL links:

DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

DPCD links:

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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=0.28216606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLL	NM_001174084.2 linkuse as main transcript	c.1309G>A	p.Gly437Ser	missense_variant	8/9	ENST00000370162.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLL	ENST00000370162.8 linkuse as main transcript	c.1309G>A	p.Gly437Ser	missense_variant	8/9	1	NM_001174084.2	P1	Q9UGP5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

251308

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

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:

0.00

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461742

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 05, 2021

The c.1309G>A (p.G437S) alteration is located in exon 8 (coding exon 7) of the POLL gene. This alteration results from a G to A substitution at nucleotide position 1309, causing the glycine (G) at amino acid position 437 to be replaced by a serine (S). 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

0.18

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

T;T;.;T;T;.;T;T;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;.;D;.;D;D;D;D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.57

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-4.2

D;D;D;D;D;.;D;D;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.017

D;D;T;D;D;.;D;D;D

Sift4G

Benign

0.41

T;T;T;T;T;T;T;.;T

Polyphen

0.97

D;D;P;D;.;.;D;.;.

Vest4

0.75

MutPred

0.28

.;Loss of catalytic residue at G437 (P = 0.0488);.;Loss of catalytic residue at G437 (P = 0.0488);.;.;Loss of catalytic residue at G437 (P = 0.0488);.;.;

MVP

0.80

MPC

0.68

ClinPred

0.73

GERP RS

5.6

Varity_R

0.67

gMVP

0.72

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