chr10-101580302-C-T
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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
NM_001174084.2 missense
Scores
4
6
8
Clinical Significance
Conservation
PhyloP100: 7.52
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]
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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 | 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 | c.1309G>A | p.Gly437Ser | missense_variant | 8/9 | 1 | NM_001174084.2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251308Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135844
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461742Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727178
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ExAC
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4
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T;.;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D;.;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;.;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;T;D;D;.;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;.;T
Polyphen
D;D;P;D;.;.;D;.;.
Vest4
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
MPC
0.68
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at