Variant 7-104200826-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002553.4(ORC5):c.298A>G(p.Asn100Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000233 in 1,460,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ORC5
NM_002553.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

Variant links:

Genes affected

ORC5 (HGNC:8491): (origin recognition complex subunit 5) The origin recognition complex (ORC) is a highly conserved six subunit 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. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Oct 2010]

ORC5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ORC5	NM_002553.4 link	c.298A>G	p.Asn100Asp	missense_variant	3/14	ENST00000297431.9	NP_002544.1	O43913-1A4D0P7Q53FC8
ORC5	NM_181747.4 link	c.298A>G	p.Asn100Asp	missense_variant	3/9		NP_859531.1	O43913-2Q53FC8
ORC5	XM_011516273.4 link	c.298A>G	p.Asn100Asp	missense_variant	3/7		XP_011514575.1
ORC5	XM_047420431.1 link	c.298A>G	p.Asn100Asp	missense_variant	3/8		XP_047276387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ORC5	ENST00000297431.9 link	c.298A>G	p.Asn100Asp	missense_variant	3/14	1	NM_002553.4	ENSP00000297431.4		O43913-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250738

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460758

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.298A>G (p.N100D) alteration is located in exon 3 (coding exon 3) of the ORC5 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the asparagine (N) at amino acid position 100 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.092

Sift

Benign

0.59

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.90

P;D

Vest4

0.80

MutPred

0.40

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.34

MPC

0.31

ClinPred

0.56

GERP RS

5.7

Varity_R

0.83

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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