rs16879646

Variant names:

• chr6-87636651-T-C
• rs16879646
• NM_012381.4:c.1382+165T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC3	NM_012381.4	c.1382+165T>C		intron_variant	Intron 13 of 19	ENST00000392844.8	NP_036513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8	c.1382+165T>C		intron_variant	Intron 13 of 19	1	NM_012381.4	ENSP00000376586.3
ORC3	ENST00000257789.4	c.1382+165T>C		intron_variant	Intron 13 of 19	1		ENSP00000257789.4
ORC3	ENST00000546266.5	c.953+165T>C		intron_variant	Intron 12 of 18	2		ENSP00000444695.1
ORC3	ENST00000681069.1	n.1415+165T>C		intron_variant	Intron 13 of 14

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11370 AN: 152200 Hom.: 436 Cov.: 32

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.: 32 AF XY: 0.0753 AC XY: 5606 AN XY: 74486

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.0675

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.0953

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0760 Hom.: 466

Bravo AF: 0.0711

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16879646; hg19: chr6-88346369;