NM_012381.4:c.1186-5811T>C

Variant names:

• chr6-87629034-T-C
• rs7755167
• NM_012381.4:c.1186-5811T>C

Variant summary

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

The NM_012381.4(ORC3):​c.1186-5811T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,920 control chromosomes in the GnomAD database, including 27,949 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 (27949 hom., cov: 32)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 9 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 = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC3	NM_012381.4	c.1186-5811T>C		intron_variant	Intron 11 of 19	ENST00000392844.8	NP_036513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8	c.1186-5811T>C		intron_variant	Intron 11 of 19	1	NM_012381.4	ENSP00000376586.3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91026 AN: 151802 Hom.: 27902 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.600 AC: 91138 AN: 151920 Hom.: 27949 Cov.: 32 AF XY: 0.599 AC XY: 44489 AN XY: 74246

African (AFR) AF: 0.719 AC: 29825 AN: 41464

American (AMR) AF: 0.674 AC: 10290 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3464

East Asian (EAS) AF: 0.562 AC: 2902 AN: 5160

South Asian (SAS) AF: 0.574 AC: 2765 AN: 4814

European-Finnish (FIN) AF: 0.523 AC: 5495 AN: 10514

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36210 AN: 67920

Other (OTH) AF: 0.592 AC: 1249 AN: 2110

Alfa AF: 0.550 Hom.: 16237

Bravo AF: 0.619

Asia WGS AF: 0.635 AC: 2210 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	8.1
DANN	Benign	0.86
PhyloP100		0.23
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: rs7755167; hg19: chr6-88338752;