rs6930600

Variant names:

• chr6-87640069-G-A
• rs6930600
• NM_012381.4:c.1382+3583G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012381.4(ORC3):​c.1382+3583G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,870 control chromosomes in the GnomAD database, including 27,891 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 0.60 (27891 hom., cov: 31)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 8 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	NM_012381.4	MANE Select	c.1382+3583G>A		intron	N/A	NP_036513.2
	ORC3	NM_181837.3		c.1382+3583G>A		intron	N/A	NP_862820.1	Q9UBD5-2
	ORC3	NM_001197259.2		c.953+3583G>A		intron	N/A	NP_001184188.1	Q9UBD5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORC3	ENST00000392844.8	TSL:1 MANE Select	c.1382+3583G>A		intron	N/A	ENSP00000376586.3	Q9UBD5-1
	ORC3	ENST00000257789.4	TSL:1	c.1382+3583G>A		intron	N/A	ENSP00000257789.4	Q9UBD5-2
	ORC3	ENST00000911372.1		c.1379+3583G>A		intron	N/A	ENSP00000581431.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90908 AN: 151752 Hom.: 27844 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.599 AC: 91020 AN: 151870 Hom.: 27891 Cov.: 31 AF XY: 0.598 AC XY: 44424 AN XY: 74228

African (AFR) AF: 0.718 AC: 29729 AN: 41380

American (AMR) AF: 0.674 AC: 10273 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2894 AN: 5138

South Asian (SAS) AF: 0.574 AC: 2764 AN: 4814

European-Finnish (FIN) AF: 0.519 AC: 5470 AN: 10534

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.533 AC: 36241 AN: 67972

Other (OTH) AF: 0.591 AC: 1245 AN: 2106

Alfa AF: 0.552 Hom.: 11943

Bravo AF: 0.619

Asia WGS AF: 0.635 AC: 2211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6930600; hg19: chr6-88349787;