10-101579710-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001174084.2(POLL):ā€‹c.1471A>Gā€‹(p.Ile491Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,613,750 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.0010 ( 1 hom., cov: 32)
Exomes š‘“: 0.00011 ( 1 hom. )

Consequence

POLL
NM_001174084.2 missense

Scores

1
4
14

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.46
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010877073).
BP6
Variant 10-101579710-T-C is Benign according to our data. Variant chr10-101579710-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041609.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POLLNM_001174084.2 linkuse as main transcriptc.1471A>G p.Ile491Val missense_variant 9/9 ENST00000370162.8 NP_001167555.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POLLENST00000370162.8 linkuse as main transcriptc.1471A>G p.Ile491Val missense_variant 9/91 NM_001174084.2 ENSP00000359181 P1Q9UGP5-1

Frequencies

GnomAD3 genomes
AF:
0.00102
AC:
155
AN:
152026
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00357
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000275
AC:
69
AN:
251042
Hom.:
1
AF XY:
0.000199
AC XY:
27
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.00394
Gnomad AMR exome
AF:
0.000145
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:
0.00
GnomAD4 exome
AF:
0.000112
AC:
163
AN:
1461606
Hom.:
1
Cov.:
32
AF XY:
0.0000990
AC XY:
72
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.00427
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.00101
AC:
154
AN:
152144
Hom.:
1
Cov.:
32
AF XY:
0.00105
AC XY:
78
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00354
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000301
Hom.:
1
Bravo
AF:
0.00117
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000321
AC:
39
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

POLL-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 30, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;T;.;T;T;.;T;T;T
Eigen
Benign
-0.016
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.91
D;.;D;.;D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.011
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
3.0
.;M;.;M;.;.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.79
N;N;N;N;N;.;N;N;N
REVEL
Benign
0.10
Sift
Benign
0.11
T;T;T;T;T;.;T;D;T
Sift4G
Benign
0.20
T;T;T;T;T;T;T;.;T
Polyphen
0.014
B;B;B;B;.;.;B;.;.
Vest4
0.15
MVP
0.18
MPC
0.14
ClinPred
0.071
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.22
gMVP
0.40

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs138242344; hg19: chr10-103339467; API