Variant 6-87590295-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.502

Variant links:

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]

ORC3 links:

ORC3 (HGNC:):

ORC3 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
ORC3	NM_012381.4 linkuse as main transcript	c.24+103A>G		intron_variant		ENST00000392844.8	NP_036513.2	Q9UBD5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8 linkuse as main transcript	c.24+103A>G		intron_variant		1	NM_012381.4	ENSP00000376586.3		Q9UBD5-1

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92495

AN:

151948

Hom.:

28976

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.608

AC XY:

45170

AN XY:

74324

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over