6-87590295-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012381.4(ORC3):c.24+103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,254,686 control chromosomes in the GnomAD database, including 197,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (29024 hom., cov: 33)
  • Exomes 𝑓: 0.55 (168786 hom.)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-87590295-A-G is Benign according to our data. Variant chr6-87590295-A-G is described in ClinVar as [Benign]. Clinvar id is 1273619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ORC3	NM_012381.4	c.24+103A>G		intron_variant		ENST00000392844.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ORC3	ENST00000392844.8	c.24+103A>G		intron_variant		1	NM_012381.4	A1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92495 AN: 151948 Hom.: 28976 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.549 AC: 605637 AN: 1102620 Hom.: 168786 AF XY: 0.547 AC XY: 308805 AN XY: 564182

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.709

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.533

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.609 AC: 92608 AN: 152066 Hom.: 29024 Cov.: 33 AF XY: 0.608 AC XY: 45170 AN XY: 74324

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.597

Alfa AF: 0.569 Hom.: 3539

Bravo AF: 0.629

Asia WGS AF: 0.634 AC: 2203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	7.5
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs9450752; hg19: chr6-88300013; COSMIC: COSV57638290; COSMIC: COSV57638290;