19-50406256-G-C

Variant names:

• chr19-50406256-G-C
• NM_002691.4:c.1317G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002691.4(POLD1):​c.1317G>C​(p.Lys439Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

ACMG classification

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=0.3293207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.1317G>C	p.Lys439Asn	missense_variant	Exon 11 of 27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.1317G>C	p.Lys439Asn	missense_variant	Exon 11 of 27	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.;.;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;.;.;M
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D;.;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;.;.;.
Sift4G	Benign	0.084	T;T;T;T
Polyphen		0.032	B;.;.;B
Vest4		0.33
MutPred		0.58		Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);
MVP		0.54
MPC		1.5
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.85
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: chr19-50909513;