6-87651299-G-A

Position:

• chr6-87651299-G-A

Variant summary

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

The NM_012381.4(ORC3):​c.1383-1817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 455,966 control chromosomes in the GnomAD database, including 39,612 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 (12351 hom., cov: 32)
  • Exomes 𝑓: 0.42 (27261 hom.)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

ORC3 (HGNC:8489): (origin recognition complex subunit 3) The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. Studies of a similar gene in Drosophila suggested a possible role of this protein in neuronal proliferation and olfactory memory. Alternatively spliced transcript variants encoding distinct isoforms have been reported for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC3	NM_012381.4	c.1383-1817G>A		intron_variant		ENST00000392844.8	NP_036513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8	c.1383-1817G>A		intron_variant		1	NM_012381.4	ENSP00000376586	A1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60946 AN: 151896 Hom.: 12331 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.432 AC: 55426 AN: 128352 Hom.: 12269 AF XY: 0.428 AC XY: 30061 AN XY: 70296

Gnomad AFR exome AF: 0.381

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.381

Gnomad EAS exome AF: 0.386

Gnomad SAS exome AF: 0.449

Gnomad FIN exome AF: 0.429

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.418 AC: 127192 AN: 303952 Hom.: 27261 Cov.: 0 AF XY: 0.418 AC XY: 72403 AN XY: 173068

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.446

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.416

GnomAD4 genome AF: 0.401 AC: 60998 AN: 152014 Hom.: 12351 Cov.: 32 AF XY: 0.402 AC XY: 29884 AN XY: 74274

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.401

Alfa AF: 0.396 Hom.: 7486

Bravo AF: 0.405

Asia WGS AF: 0.453 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.081
DANN	Benign	0.51

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: rs7772351; hg19: chr6-88361017;