dbSNP rs16879646: ORC3:c.1382+165T>C (chr6-87636651-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012381.4(ORC3):c.1382+165T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,318 control chromosomes in the GnomAD database, including 443 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 0.075 ( 443 hom., cov: 32)

Consequence

ORC3
NM_012381.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380

Publications

9 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0883 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ORC3	NM_012381.4	MANE Select	c.1382+165T>C	intron	N/A	NP_036513.2
ORC3	NM_181837.3		c.1382+165T>C	intron	N/A	NP_862820.1	Q9UBD5-2
ORC3	NM_001197259.2		c.953+165T>C	intron	N/A	NP_001184188.1	Q9UBD5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ORC3	ENST00000392844.8	TSL:1 MANE Select	c.1382+165T>C	intron	N/A	ENSP00000376586.3	Q9UBD5-1
ORC3	ENST00000257789.4	TSL:1	c.1382+165T>C	intron	N/A	ENSP00000257789.4	Q9UBD5-2
ORC3	ENST00000911372.1		c.1379+165T>C	intron	N/A	ENSP00000581431.1

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11370

AN:

152200

Hom.:

436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0674

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.0950

Gnomad SAS

AF:

0.0937

Gnomad FIN

AF:

0.0931

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0784

Gnomad OTH

AF:

0.0693

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

GnomAD4 genome

AF:

0.0748

AC:

11391

AN:

152318

Hom.:

443

Cov.:

AF XY:

0.0753

AC XY:

5606

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0654

AC:

2718

AN:

41568

American (AMR)

AF:

0.0675

AC:

1033

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

169

AN:

3472

East Asian (EAS)

AF:

0.0953

AC:

494

AN:

5186

South Asian (SAS)

AF:

0.0927

AC:

448

AN:

4832

European-Finnish (FIN)

AF:

0.0931

AC:

987

AN:

10604

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0785

AC:

5337

AN:

68030

Other (OTH)

AF:

0.0771

AC:

163

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

543

1086

1630

2173

2716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0753

Hom.:

602

Bravo

AF:

0.0711

Asia WGS

AF:

0.140

AC:

486

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.6

(source)

DANN

Benign

0.80

PhyloP100

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over