Variant 1-58534306-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145243.5(OMA1):c.755T>C(p.Met252Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 856,292 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 (★).

Frequency

Genomes: 𝑓 0.00064 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 10 hom. )

Consequence

OMA1
NM_145243.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.46

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009375572).

BP6

Variant 1-58534306-A-G is Benign according to our data. Variant chr1-58534306-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 729080.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5 linkuse as main transcript	c.755T>C	p.Met252Thr	missense_variant	4/9	ENST00000371226.8
DAB1	NM_001379461.1 linkuse as main transcript	c.-729-6971T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8 linkuse as main transcript	c.755T>C	p.Met252Thr	missense_variant	4/9	1	NM_145243.5	P1	Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00111

AC:

259

AN:

233936

Hom.:

AF XY:

0.00130

AC XY:

165

AN XY:

126456

show subpopulations

Gnomad AFR exome

AF:

0.000378

Gnomad AMR exome

AF:

0.000313

Gnomad ASJ exome

AF:

0.00425

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00609

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.00102

AC:

715

AN:

703974

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

478

AN XY:

375504

show subpopulations

Gnomad4 AFR exome

AF:

0.000265

Gnomad4 AMR exome

AF:

0.000364

Gnomad4 ASJ exome

AF:

0.00400

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000364

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.000643

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00580

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000544

Hom.:

Bravo

AF:

0.000627

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00120

AC:

146

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000297

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

Dec 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0093

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.;.

MutationTaster

Benign

0.76

D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

D;D;D;N

REVEL

Benign

0.16

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0090

D;.;.;.

Polyphen

0.58

P;.;.;.

Vest4

0.62

MVP

0.18

MPC

0.27

ClinPred

0.030

GERP RS

4.9

Varity_R

0.40

gMVP

0.64

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