rs14419

Positions:

• chr9-113408279-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017443.5(POLE3):​c.*532C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,080 control chromosomes in the GnomAD database, including 10,775 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 0.37 (10771 hom., cov: 32)
  • Exomes 𝑓: 0.28 (4 hom.)
• Consequence: POLE3 NM_017443.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

Genes affected

POLE3 (HGNC:13546): (DNA polymerase epsilon 3, accessory subunit) POLE3 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLE3	NM_017443.5	c.*532C>T		3_prime_UTR_variant	5/5	ENST00000374171.5	NP_059139.3
POLE3	NM_001278255.1	c.*532C>T		3_prime_UTR_variant	5/5		NP_001265184.1
POLE3	NR_027261.2	n.1057C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLE3	ENST00000374171.5	c.*532C>T		3_prime_UTR_variant	5/5	2	NM_017443.5	ENSP00000363286	P1
POLE3	ENST00000374169.7	c.*532C>T		3_prime_UTR_variant	4/4	1		ENSP00000363284	P1
POLE3	ENST00000479871.1	n.1352C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55535 AN: 151862 Hom.: 10751 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.280 AC: 28 AN: 100 Hom.: 4 Cov.: 0 AF XY: 0.250 AC XY: 17 AN XY: 68

Gnomad4 AMR exome AF: 0.100

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.366 AC: 55600 AN: 151980 Hom.: 10771 Cov.: 32 AF XY: 0.360 AC XY: 26767 AN XY: 74270

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0643

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.321

Alfa AF: 0.363 Hom.: 5408

Bravo AF: 0.356

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs14419; hg19: chr9-116170559;