chr1-58539090-G-A

Position:

chr1-58539090-G-A

Variant summary

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

The NM_145243.5(OMA1):c.205C>T(p.His69Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 872,884 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 11 hom. )

Consequence

OMA1
NM_145243.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.784

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=0.0035673082).

BP6

Variant 1-58539090-G-A is Benign according to our data. Variant chr1-58539090-G-A is described in ClinVar as [Benign]. Clinvar id is 767673.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00758 (1154/152260) while in subpopulation AFR AF= 0.0196 (815/41572). AF 95% confidence interval is 0.0185. There are 7 homozygotes in gnomad4. There are 555 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5 linkuse as main transcript	c.205C>T	p.His69Tyr	missense_variant	2/9	ENST00000371226.8
DAB1	NM_001379461.1 linkuse as main transcript	c.-730+7613C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8 linkuse as main transcript	c.205C>T	p.His69Tyr	missense_variant	2/9	1	NM_145243.5	P1	Q96E52-1

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00354

AC:

889

AN:

251126

Hom.:

AF XY:

0.00307

AC XY:

417

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0214

Gnomad AMR exome

AF:

0.00613

Gnomad ASJ exome

AF:

0.00665

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00173

Gnomad OTH exome

AF:

0.00719

GnomAD4 exome

AF:

0.00264

AC:

1904

AN:

720624

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

935

AN XY:

384664

show subpopulations

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.00624

Gnomad4 ASJ exome

AF:

0.00763

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000823

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00611

GnomAD4 genome

AF:

0.00758

AC:

1154

AN:

152260

Hom.:

Cov.:

AF XY:

0.00745

AC XY:

555

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.00807

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00998

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00944

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00348

AC:

422

Asia WGS

AF:

0.00231

AC:

AN:

3478

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

Aug 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.0

DANN

Benign

0.39

DEOGEN2

Benign

0.0032

T;T;T;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.57

T;T;T;T;T;T

MetaRNN

Benign

0.0036

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;.;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.28

N;N;N;N;N;.

REVEL

Benign

0.038

Sift

Benign

0.65

T;T;T;T;T;.

Sift4G

Benign

1.0

T;.;.;.;.;.

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.072

MVP

0.072

MPC

0.071

ClinPred

0.00055

GERP RS

0.47

Varity_R

0.014

gMVP

0.19

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