rs28381552

chr6-87667331-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_012381.4(ORC3):c.*208T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 428,988 control chromosomes in the GnomAD database, including 377 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 0.032 (98 hom., cov: 32)
  • Exomes 𝑓: 0.039 (279 hom.)
• Consequence: ORC3 NM_012381.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0316 (4815/152312) while in subpopulation NFE AF= 0.0472 (3208/68018). AF 95% confidence interval is 0.0458. There are 98 homozygotes in gnomad4. There are 2275 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 98 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC3	NM_012381.4	c.*208T>C		3_prime_UTR_variant	20/20	ENST00000392844.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC3	ENST00000392844.8	c.*208T>C		3_prime_UTR_variant	20/20	1	NM_012381.4	A1
ORC3	ENST00000257789.4	c.*208T>C		3_prime_UTR_variant	20/20	1		P4
ORC3	ENST00000546266.5	c.*208T>C		3_prime_UTR_variant	19/19	2

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4819 AN: 152194 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.00731

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0206

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.0394 AC: 10909 AN: 276676 Hom.: 279 Cov.: 0 AF XY: 0.0394 AC XY: 5600 AN XY: 142032

Gnomad4 AFR exome AF: 0.00927

Gnomad4 AMR exome AF: 0.0394

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0208

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0477

Gnomad4 OTH exome AF: 0.0404

GnomAD4 genome AF: 0.0316 AC: 4815 AN: 152312 Hom.: 98 Cov.: 32 AF XY: 0.0305 AC XY: 2275 AN XY: 74470

Gnomad4 AFR AF: 0.00729

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0150

Gnomad4 SAS AF: 0.0213

Gnomad4 FIN AF: 0.0206

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0475 Hom.: 190

Bravo AF: 0.0329

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.1
Dann	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs28381552; hg19: chr6-88377049;