15-41332451-C-T

Position:

• chr15-41332451-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007280.2(OIP5):​c.111G>A​(p.Met37Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OIP5 NM_007280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.425

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]

ENSG00000285920 (HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115852684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OIP5	NM_007280.2	c.111G>A	p.Met37Ile	missense_variant	1/5	ENST00000220514.8	NP_009211.1
OIP5	NM_001317860.2	c.111G>A	p.Met37Ile	missense_variant	1/4		NP_001304789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OIP5	ENST00000220514.8	c.111G>A	p.Met37Ile	missense_variant	1/5	1	NM_007280.2	ENSP00000220514.3
ENSG00000285920	ENST00000661438.1	c.-507C>T		5_prime_UTR_variant	2/12			ENSP00000499503.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.111G>A (p.M37I) alteration is located in exon 1 (coding exon 1) of the OIP5 gene. This alteration results from a G to A substitution at nucleotide position 111, causing the methionine (M) at amino acid position 37 to be replaced by an isoleucine (I). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.033
Sift	Benign	0.036	D
Sift4G	Benign	0.13	T
Polyphen		0.0040	B
Vest4		0.22
MutPred		0.22		Gain of sheet (P = 0.0149);
MVP		0.31
MPC		0.074
ClinPred		0.35	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.088

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-41624649;