19-50417187-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002691.4(POLD1):​c.3136G>C​(p.Ala1046Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1046S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

POLD1
NM_002691.4 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.488
Variant links:
Genes affected
POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POLD1NM_002691.4 linkuse as main transcriptc.3136G>C p.Ala1046Pro missense_variant 26/27 ENST00000440232.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POLD1ENST00000440232.7 linkuse as main transcriptc.3136G>C p.Ala1046Pro missense_variant 26/271 NM_002691.4 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.79
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
T;.;.;T
Eigen
Benign
0.034
Eigen_PC
Benign
-0.046
FATHMM_MKL
Benign
0.26
N
LIST_S2
Uncertain
0.94
.;.;D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.4
M;.;.;M
MutationTaster
Benign
0.63
N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.7
N;.;.;.
REVEL
Benign
0.13
Sift
Benign
0.089
T;.;.;.
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.62
P;.;.;P
Vest4
0.61
MutPred
0.50
Gain of disorder (P = 0.0344);.;.;Gain of disorder (P = 0.0344);
MVP
0.63
MPC
1.6
ClinPred
0.93
D
GERP RS
3.1
Varity_R
0.86
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50920444; API