chr1-58530648-C-A

Position:

• chr1-58530648-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.61

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]

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]

OMA1 (HGNC:):

ACMG classification

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	Protein	UniProt
OMA1	NM_145243.5	c.1093G>T	p.Asp365Tyr	missense_variant	6/9	ENST00000371226.8	NP_660286.1
DAB1	NM_001379461.1	c.-729-3313G>T		intron_variant			NP_001366390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OMA1	ENST00000371226.8	c.1093G>T	p.Asp365Tyr	missense_variant	6/9	1	NM_145243.5	ENSP00000360270.3

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152214 Hom.: 0 Cov.: 33

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.: 2 AF XY: 0.00345 AC XY: 468 AN XY: 135782

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.: 11 Cov.: 0 AF XY: 0.00363 AC XY: 1398 AN XY: 384616

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.: 0 Cov.: 33 AF XY: 0.00307 AC XY: 229 AN XY: 74496

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.: 3

Bravo AF: 0.00326

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00326 AC: 396

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00486

EpiControl AF: 0.00421

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.079	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.9	M
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.93
MVP		0.62
MPC		0.43
ClinPred		0.032	T
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

Other links and lift over

dbSNP: rs77980955; hg19: chr1-58996320; COSMIC: COSV105265620; COSMIC: COSV105265620;