Variant chr15-41332492-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007280.2(OIP5):c.70A>C(p.Thr24Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000083 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

OIP5
NM_007280.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

OIP5 (HGNC:20300): (Opa interacting protein 5) The protein encoded by this gene localizes to centromeres, where it is essential for recruitment of CENP-A through the mediator Holliday junction recognition protein. Expression of this gene is upregulated in several cancers, making it a putative therapeutic target. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

OIP5 links:

NUSAP1 (HGNC:18538): (nucleolar and spindle associated protein 1) NUSAP1 is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization (Raemaekers et al., 2003 [PubMed 12963707]).[supplied by OMIM, Jun 2009]

NUSAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048686802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OIP5	NM_007280.2 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	1/5	ENST00000220514.8	NP_009211.1
OIP5	NM_001317860.2 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	1/4		NP_001304789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OIP5	ENST00000220514.8 linkuse as main transcript	c.70A>C	p.Thr24Pro	missense_variant	1/5	1	NM_007280.2	ENSP00000220514	P1
NUSAP1	ENST00000668273.1 linkuse as main transcript	c.-466T>G		5_prime_UTR_variant	2/12			ENSP00000499238	P4	Q9BXS6-1
OIP5	ENST00000560640.1 linkuse as main transcript			upstream_gene_variant		3		ENSP00000452851

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249550

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135058

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:

0.0000712

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000869

AC:

127

AN:

1461710

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000107

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000156

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

May 27, 2022

The c.70A>C (p.T24P) alteration is located in exon 1 (coding exon 1) of the OIP5 gene. This alteration results from a A to C substitution at nucleotide position 70, causing the threonine (T) at amino acid position 24 to be replaced by a proline (P). 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

0.070

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.5

DANN

Benign

0.53

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.27

M_CAP

Benign

0.0035

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.49

REVEL

Benign

0.0080

Sift

Benign

0.19

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.089

MutPred

0.16

Loss of phosphorylation at T24 (P = 0.0276);

MVP

0.095

MPC

0.084

ClinPred

0.043

GERP RS

-2.2

Varity_R

0.10

gMVP

0.14

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

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