Variant 1-58536647-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_145243.5(OMA1):c.595T>C(p.Leu199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00759 in 872,864 control chromosomes in the GnomAD database, including 279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 177 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 102 hom. )

Consequence

OMA1
NM_145243.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.296

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 1-58536647-A-G is Benign according to our data. Variant chr1-58536647-A-G is described in ClinVar as [Benign]. Clinvar id is 780241.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.296 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5 linkuse as main transcript	c.595T>C	p.Leu199=	synonymous_variant	3/9	ENST00000371226.8
DAB1	NM_001379461.1 linkuse as main transcript	c.-729-9312T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8 linkuse as main transcript	c.595T>C	p.Leu199=	synonymous_variant	3/9	1	NM_145243.5	P1	Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4084

AN:

152202

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0927

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.00696

AC:

1748

AN:

251326

Hom.:

AF XY:

0.00481

AC XY:

654

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.0948

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00440

GnomAD4 exome

AF:

0.00352

AC:

2533

AN:

720544

Hom.:

102

Cov.:

AF XY:

0.00290

AC XY:

1114

AN XY:

384626

show subpopulations

Gnomad4 AFR exome

AF:

0.0978

Gnomad4 AMR exome

AF:

0.00476

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.00608

GnomAD4 genome

AF:

0.0269

AC:

4095

AN:

152320

Hom.:

177

Cov.:

AF XY:

0.0261

AC XY:

1946

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0927

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0305

Asia WGS

AF:

0.00520

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

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

Jun 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.8

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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