Variant 10-96346071-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033207.5(OPALIN):c.296A>G(p.Gln99Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,836 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: 0.0000027 ( 0 hom. )

Consequence

OPALIN
NM_033207.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

OPALIN (HGNC:20707): (oligodendrocytic myelin paranodal and inner loop protein) Predicted to be involved in regulation of oligodendrocyte differentiation. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

OPALIN links:

OPALIN (HGNC:):

OPALIN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10117644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPALIN	NM_033207.5 linkuse as main transcript	c.296A>G	p.Gln99Arg	missense_variant	6/6	ENST00000371172.8	NP_149984.1	Q96PE5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPALIN	ENST00000371172.8 linkuse as main transcript	c.296A>G	p.Gln99Arg	missense_variant	6/6	1	NM_033207.5	ENSP00000360214.3		Q96PE5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251224

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135768

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727218

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Mar 14, 2023

The c.296A>G (p.Q99R) alteration is located in exon 6 (coding exon 6) of the OPALIN gene. This alteration results from a A to G substitution at nucleotide position 296, causing the glutamine (Q) at amino acid position 99 to be replaced by an arginine (R). 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

0.083

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

T;.;.;.;.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.81

T;T;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.10

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.9

D;.;.;D;.;.

REVEL

Benign

0.023

Sift

Uncertain

0.015

D;.;.;D;.;.

Sift4G

Benign

0.065

T;T;T;T;T;T

Polyphen

0.14

B;.;.;.;.;.

Vest4

0.11

MutPred

0.18

Gain of MoRF binding (P = 0.0141);.;.;.;.;.;

MVP

0.040

MPC

0.48

ClinPred

0.88

GERP RS

1.7

Varity_R

0.14

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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