chr15-41332524-G-A

Position:

• chr15-41332524-G-A

Variant summary

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

The NM_007280.2(OIP5):​c.38C>T​(p.Ala13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OIP5 NM_007280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0920

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]

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=0.07869053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OIP5	NM_007280.2	c.38C>T	p.Ala13Val	missense_variant	1/5	ENST00000220514.8	NP_009211.1
OIP5	NM_001317860.2	c.38C>T	p.Ala13Val	missense_variant	1/4		NP_001304789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OIP5	ENST00000220514.8	c.38C>T	p.Ala13Val	missense_variant	1/5	1	NM_007280.2	ENSP00000220514	P1
NUSAP1	ENST00000668273.1	c.-434G>A		5_prime_UTR_variant	2/12			ENSP00000499238	P4
OIP5	ENST00000560640.1			upstream_gene_variant		3		ENSP00000452851

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460088 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726442

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

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

Dec 21, 2022

The c.38C>T (p.A13V) alteration is located in exon 1 (coding exon 1) of the OIP5 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the alanine (A) at amino acid position 13 to be replaced by a valine (V). 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	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.11
Sift	Benign	0.30	T
Sift4G	Uncertain	0.057	T
Polyphen		0.25	B
Vest4		0.13
MutPred		0.16		Loss of relative solvent accessibility (P = 0.0414);
MVP		0.24
MPC		0.066
ClinPred		0.21	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1160777283; hg19: chr15-41624722;