Variant 1-58534181-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_145243.5(OMA1):c.880A>G(p.Ile294Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 871,604 control chromosomes in the GnomAD database, including 18 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 13 hom. )

Consequence

OMA1
NM_145243.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.781

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023922026).

BP6

Variant 1-58534181-T-C is Benign according to our data. Variant chr1-58534181-T-C is described in ClinVar as [Benign]. Clinvar id is 773636.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00173 (263/152348) while in subpopulation EAS AF= 0.0291 (151/5188). AF 95% confidence interval is 0.0253. There are 5 homozygotes in gnomad4. There are 153 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5 linkuse as main transcript	c.880A>G	p.Ile294Val	missense_variant	4/9	ENST00000371226.8
DAB1	NM_001379461.1 linkuse as main transcript	c.-729-6846A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8 linkuse as main transcript	c.880A>G	p.Ile294Val	missense_variant	4/9	1	NM_145243.5	P1	Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

262

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.0288

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00300

AC:

750

AN:

249724

Hom.:

AF XY:

0.00298

AC XY:

402

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000878

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0280

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00199

AC:

1432

AN:

719256

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

768

AN XY:

383852

show subpopulations

Gnomad4 AFR exome

AF:

0.000101

Gnomad4 AMR exome

AF:

0.0000918

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.0187

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00173

Gnomad4 NFE exome

AF:

0.000321

Gnomad4 OTH exome

AF:

0.00414

GnomAD4 genome

AF:

0.00173

AC:

263

AN:

152348

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

153

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.0291

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00162

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00250

AC:

303

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.7

DANN

Benign

0.70

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

0.19

N;N

REVEL

Benign

0.061

Sift

Benign

0.28

T;T

Sift4G

Benign

0.28

T;.

Polyphen

0.0

B;.

Vest4

0.091

MVP

0.18

MPC

0.054

ClinPred

0.0024

GERP RS

2.7

Varity_R

0.022

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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