Variant 1-58530648-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_145243.5(OMA1):c.1093G>T(p.Asp365Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00361 in 872,802 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0034 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 11 hom. )

Consequence

OMA1
NM_145243.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.61

Variant links:

Genes affected

OMA1 (HGNC:29661): (OMA1 zinc metallopeptidase) Enables metalloendopeptidase activity. Involved in several processes, including HRI-mediated signaling; proteolysis; and regulation of mitochondrion organization. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

OMA1 links:

DAB1 (HGNC:2661): (DAB adaptor protein 1) The laminar organization of multiple neuronal types in the cerebral cortex is required for normal cognitive function. In mice, the disabled-1 gene plays a central role in brain development, directing the migration of cortical neurons past previously formed neurons to reach their proper layer. This gene is similar to disabled-1, and the protein encoded by this gene is thought to be a signal transducer that interacts with protein kinase pathways to regulate neuronal positioning in the developing brain. [provided by RefSeq, Jan 2017]

DAB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07886812).

BP6

Variant 1-58530648-C-A is Benign according to our data. Variant chr1-58530648-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 713749.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5 linkuse as main transcript	c.1093G>T	p.Asp365Tyr	missense_variant	6/9	ENST00000371226.8
DAB1	NM_001379461.1 linkuse as main transcript	c.-729-3313G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8 linkuse as main transcript	c.1093G>T	p.Asp365Tyr	missense_variant	6/9	1	NM_145243.5	P1	Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

523

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00536

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00333

AC:

837

AN:

251234

Hom.:

AF XY:

0.00345

AC XY:

468

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00216

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.00492

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00365

AC:

2633

AN:

720470

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

1398

AN XY:

384616

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.00307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00215

Gnomad4 FIN exome

AF:

0.00284

Gnomad4 NFE exome

AF:

0.00468

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152332

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

229

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00535

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.00326

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00326

AC:

396

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00486

EpiControl

AF:

0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.079

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.93

MVP

0.62

MPC

0.43

ClinPred

0.032

GERP RS

5.1

Varity_R

0.86

gMVP

0.88

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

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