6-87620224-C-T

Variant names:

• chr6-87620224-C-T
• rs13213285
• NM_012381.4:c.988-1130C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012381.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	NM_012381.4	MANE Select	c.988-1130C>T		intron	N/A	NP_036513.2
	ORC3	NM_181837.3		c.988-1130C>T		intron	N/A	NP_862820.1
	ORC3	NM_001197259.2		c.559-1130C>T		intron	N/A	NP_001184188.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	ENST00000392844.8	TSL:1 MANE Select	c.988-1130C>T		intron	N/A	ENSP00000376586.3
	ORC3	ENST00000257789.4	TSL:1	c.988-1130C>T		intron	N/A	ENSP00000257789.4
	ORC3	ENST00000850561.1		c.988-1130C>T		intron	N/A	ENSP00000520852.1

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

African (AFR) AF: 0.121 AC: 5020 AN: 41492

American (AMR) AF: 0.0512 AC: 781 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3470

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5174

South Asian (SAS) AF: 0.0226 AC: 109 AN: 4818

European-Finnish (FIN) AF: 0.0207 AC: 219 AN: 10560

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0473 AC: 3215 AN: 67996

Other (OTH) AF: 0.0645 AC: 136 AN: 2110

Alfa AF: 0.0580 Hom.: 621

Bravo AF: 0.0709

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.7
DANN	Benign	0.63
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13213285; hg19: chr6-88329942;