19-50417200-G-T

Position:

• chr19-50417200-G-T

Variant summary

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

The NM_002691.4(POLD1):​c.3149G>T​(p.Arg1050Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,260 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: POLD1 NM_002691.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05

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/exons	MANE	Protein	UniProt
POLD1	NM_002691.4	c.3149G>T	p.Arg1050Leu	missense_variant	26/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.3149G>T	p.Arg1050Leu	missense_variant	26/27	1	NM_002691.4	ENSP00000406046.1
ENSG00000142539	ENST00000599632.1	c.356G>T	p.Arg119Leu	missense_variant	5/10	5		ENSP00000473233.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454260 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000200

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T;.;.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.63	D
LIST_S2	Pathogenic	0.99	.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M;.;.;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-4.8	D;.;.;.
REVEL	Benign	0.13
Sift	Benign	0.17	T;.;.;.
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.0030	B;.;.;B
Vest4		0.76
MutPred		0.47		Loss of MoRF binding (P = 0.0481);.;.;Loss of MoRF binding (P = 0.0481);
MVP		0.66
MPC		1.6
ClinPred		0.95	D
GERP RS		3.1
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.30
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr19-50920457;