19-50398885-G-C

Position:

• chr19-50398885-G-C

Variant summary

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

The NM_002691.4(POLD1):​c.34G>C​(p.Gly12Arg) 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. 13/21 in silico tools predict 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: 2.90

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=0.33590966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD1	NM_002691.4	c.34G>C	p.Gly12Arg	missense_variant	2/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.34G>C	p.Gly12Arg	missense_variant	2/27	1	NM_002691.4	ENSP00000406046	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;.;.;.;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	.;.;T;T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;.;.;N;.
MutationTaster	Benign	0.64	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.3	N;.;.;.;.;.
REVEL	Benign	0.082
Sift	Uncertain	0.0070	D;.;.;.;.;.
Sift4G	Benign	0.21	T;T;D;T;T;D
Polyphen		0.78	P;.;.;.;P;.
Vest4		0.48
MutPred		0.25		Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);Gain of MoRF binding (P = 0.0024);
MVP		0.58
MPC		0.22
ClinPred		0.48	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-50902142;