rs3824999

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006591.3(POLD3):​c.1007-78T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 804,116 control chromosomes in the GnomAD database, including 87,844 homozygotes. 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: 𝑓 0.40 ( 13753 hom., cov: 31)
Exomes 𝑓: 0.47 ( 74091 hom. )

Consequence

POLD3
NM_006591.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0740
Variant links:
Genes affected
POLD3 (HGNC:20932): (DNA polymerase delta 3, accessory subunit) This gene encodes the 66-kDa 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. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POLD3NM_006591.3 linkuse as main transcriptc.1007-78T>G intron_variant ENST00000263681.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POLD3ENST00000263681.7 linkuse as main transcriptc.1007-78T>G intron_variant 1 NM_006591.3 P1Q15054-1

Frequencies

GnomAD3 genomes
AF:
0.399
AC:
60678
AN:
151920
Hom.:
13758
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.175
Gnomad AMI
AF:
0.547
Gnomad AMR
AF:
0.403
Gnomad ASJ
AF:
0.618
Gnomad EAS
AF:
0.400
Gnomad SAS
AF:
0.348
Gnomad FIN
AF:
0.492
Gnomad MID
AF:
0.399
Gnomad NFE
AF:
0.511
Gnomad OTH
AF:
0.421
GnomAD4 exome
AF:
0.468
AC:
305188
AN:
652078
Hom.:
74091
AF XY:
0.467
AC XY:
163121
AN XY:
349386
show subpopulations
Gnomad4 AFR exome
AF:
0.172
Gnomad4 AMR exome
AF:
0.337
Gnomad4 ASJ exome
AF:
0.604
Gnomad4 EAS exome
AF:
0.414
Gnomad4 SAS exome
AF:
0.354
Gnomad4 FIN exome
AF:
0.489
Gnomad4 NFE exome
AF:
0.510
Gnomad4 OTH exome
AF:
0.464
GnomAD4 genome
AF:
0.399
AC:
60686
AN:
152038
Hom.:
13753
Cov.:
31
AF XY:
0.399
AC XY:
29642
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.175
Gnomad4 AMR
AF:
0.402
Gnomad4 ASJ
AF:
0.618
Gnomad4 EAS
AF:
0.401
Gnomad4 SAS
AF:
0.349
Gnomad4 FIN
AF:
0.492
Gnomad4 NFE
AF:
0.511
Gnomad4 OTH
AF:
0.417
Alfa
AF:
0.487
Hom.:
18389
Bravo
AF:
0.381
Asia WGS
AF:
0.333
AC:
1161
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
3.5
DANN
Benign
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3824999; hg19: chr11-74345550; COSMIC: COSV55245928; COSMIC: COSV55245928; API