rs13213285

chr6-87620224-C-T

Variant summary

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

The NM_012381.4(ORC3):c.988-1130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0643 in 152,090 control chromosomes in the GnomAD database, including 411 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 0.064 (411 hom., cov: 32)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC3	NM_012381.4	c.988-1130C>T		intron_variant		ENST00000392844.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC3	ENST00000392844.8	c.988-1130C>T		intron_variant		1	NM_012381.4	A1
ORC3	ENST00000257789.4	c.988-1130C>T		intron_variant		1		P4
ORC3	ENST00000546266.5	c.559-1130C>T		intron_variant		2
ORC3	ENST00000681069.1	n.1021-1130C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9781 AN: 151972 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0207

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0473

Gnomad OTH AF: 0.0651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0643 AC: 9786 AN: 152090 Hom.: 411 Cov.: 32 AF XY: 0.0627 AC XY: 4663 AN XY: 74316

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0207

Gnomad4 NFE AF: 0.0473

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0522 Hom.: 339

Bravo AF: 0.0709

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	7.7
Dann	Benign	0.63

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: rs13213285; hg19: chr6-88329942;