15-41319700-G-A

Position:

• chr15-41319700-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.470C>T​(p.Ala157Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 0.0000014 (0 hom.)
• Consequence: OIP5 NM_007280.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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-AS1 (HGNC:43563): (OIP5 antisense RNA 1) This is a conserved gene that produces a long non-coding RNA that maintains cell proliferation in embryonic stem cells. This RNA can bind to and negatively regulate the activity of multiple cellular RNAs and microRNAs, including cyclin G associated kinase and ELAV like RNA binding protein 1. [provided by RefSeq, Dec 2017]

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=0.1548965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OIP5	NM_007280.2	c.470C>T	p.Ala157Val	missense_variant	3/5	ENST00000220514.8	NP_009211.1
OIP5	NM_001317860.2	c.390-6346C>T		intron_variant			NP_001304789.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OIP5	ENST00000220514.8	c.470C>T	p.Ala157Val	missense_variant	3/5	1	NM_007280.2	ENSP00000220514	P1
OIP5-AS1	ENST00000707047.1	n.539G>A		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461546 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727092

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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 02, 2023

The c.470C>T (p.A157V) alteration is located in exon 3 (coding exon 3) of the OIP5 gene. This alteration results from a C to T substitution at nucleotide position 470, causing the alanine (A) at amino acid position 157 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	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	0.70	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.067
Sift	Benign	0.49	T
Sift4G	Benign	0.12	T
Polyphen		0.25	B
Vest4		0.35
MutPred		0.30		Loss of methylation at R159 (P = 0.072);
MVP		0.61
MPC		0.38
ClinPred		0.87	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1158514145; hg19: chr15-41611898;