Variant 10-96349778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_033207.5(OPALIN):c.121G>T(p.Ala41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,613,414 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 41 hom. )

Consequence

OPALIN
NM_033207.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010461628).

BP6

Variant 10-96349778-C-A is Benign according to our data. Variant chr10-96349778-C-A is described in ClinVar as [Benign]. Clinvar id is 791492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPALIN	NM_033207.5 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	4/6	ENST00000371172.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPALIN	ENST00000371172.8 linkuse as main transcript	c.121G>T	p.Ala41Ser	missense_variant	4/6	1	NM_033207.5	P1	Q96PE5-1

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

823

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00830

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00460

AC:

1147

AN:

249186

Hom.:

AF XY:

0.00484

AC XY:

652

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00305

Gnomad ASJ exome

AF:

0.00460

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00511

GnomAD4 exome

AF:

0.00689

AC:

10070

AN:

1461114

Hom.:

Cov.:

AF XY:

0.00682

AC XY:

4958

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.00536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.00595

Gnomad4 NFE exome

AF:

0.00806

Gnomad4 OTH exome

AF:

0.00724

GnomAD4 genome

AF:

0.00540

AC:

822

AN:

152300

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.00829

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00678

Hom.:

Bravo

AF:

0.00511

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00907

AC:

ExAC

AF:

0.00446

AC:

541

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00895

EpiControl

AF:

0.00852

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.0037

MetaRNN

Benign

0.010

T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.0

M;.;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.6

D;.;D;.;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;.;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;.;.;.;.

Vest4

0.53

MVP

0.51

MPC

0.59

ClinPred

0.022

GERP RS

5.3

Varity_R

0.61

gMVP

0.28

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