6-87660125-G-A

Variant names:

• chr6-87660125-G-A
• rs10498961
• NM_012381.4:c.1691+2107G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012381.4(ORC3):​c.1691+2107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,234 control chromosomes in the GnomAD database, including 552 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 0.083 (552 hom., cov: 32)
• Consequence: ORC3 NM_012381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 3 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.096 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORC3	NM_012381.4	c.1691+2107G>A		intron_variant	Intron 16 of 19	ENST00000392844.8	NP_036513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORC3	ENST00000392844.8	c.1691+2107G>A		intron_variant	Intron 16 of 19	1	NM_012381.4	ENSP00000376586.3
ORC3	ENST00000257789.4	c.1694+2107G>A		intron_variant	Intron 16 of 19	1		ENSP00000257789.4
ORC3	ENST00000850561.1	c.1691+2107G>A		intron_variant	Intron 16 of 19			ENSP00000520852.1
ORC3	ENST00000546266.5	c.1262+2107G>A		intron_variant	Intron 15 of 18	2		ENSP00000444695.1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12583 AN: 152116 Hom.: 545 Cov.: 32

Gnomad AFR AF: 0.0987

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0828 AC: 12601 AN: 152234 Hom.: 552 Cov.: 32 AF XY: 0.0835 AC XY: 6216 AN XY: 74430

African (AFR) AF: 0.0985 AC: 4090 AN: 41532

American (AMR) AF: 0.0667 AC: 1020 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3466

East Asian (EAS) AF: 0.0967 AC: 501 AN: 5182

South Asian (SAS) AF: 0.0910 AC: 439 AN: 4822

European-Finnish (FIN) AF: 0.0936 AC: 992 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5211 AN: 68018

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0763 Hom.: 619

Bravo AF: 0.0806

Asia WGS AF: 0.137 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.61
PhyloP100		-0.080
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10498961; hg19: chr6-88369843;