rs1060504348

Positions:

• chr19-50406229-C-G
• chr19-50406229-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002691.4(POLD1):​c.1290C>G​(p.Asn430Lys) 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. 15/21 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: 0.125

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052361965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD1	NM_002691.4	c.1290C>G	p.Asn430Lys	missense_variant	11/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.1290C>G	p.Asn430Lys	missense_variant	11/27	1	NM_002691.4	ENSP00000406046	P1

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	Benign	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.079	T;.;.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.81	.;.;T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.93	N;.;.;N
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.13	N;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.93	T;.;.;.
Sift4G	Benign	0.96	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.17
MutPred		0.59		Gain of methylation at N430 (P = 0.0184);Gain of methylation at N430 (P = 0.0184);Gain of methylation at N430 (P = 0.0184);Gain of methylation at N430 (P = 0.0184);
MVP		0.23
MPC		0.72
ClinPred		0.057	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.26

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: chr19-50909486;