NM_002691.4:c.3198C>G

Variant names:

• chr19-50417249-C-G
• NM_002691.4:c.3198C>G

Variant summary

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

The NM_002691.4(POLD1):​c.3198C>G​(p.His1066Gln) 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.

• Frequency: Genomes: not found (cov: 34)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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]

ENSG00000142539 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.3198C>G	p.His1066Gln	missense_variant	Exon 26 of 27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.3198C>G	p.His1066Gln	missense_variant	Exon 26 of 27	1	NM_002691.4	ENSP00000406046.1
ENSG00000142539	ENST00000599632.1	c.405C>G	p.His135Gln	missense_variant	Exon 5 of 10	5		ENSP00000473233.1

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	0.89
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	8.5
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;.;.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.96	.;.;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.68	D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	3.2	M;.;.;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-7.4	D;.;.;.
REVEL	Benign	0.23
Sift	Benign	0.031	D;.;.;.
Sift4G	Uncertain	0.043	D;D;D;D
Polyphen		0.82	P;.;.;P
Vest4		0.68
MutPred		0.37		Loss of catalytic residue at H1066 (P = 0.0245);.;.;Loss of catalytic residue at H1066 (P = 0.0245);
MVP		0.48
MPC		1.6
ClinPred		0.99	D
GERP RS		-2.2
Varity_R		0.74
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50920506;