1-58536610-A-C

Position:

• chr1-58536610-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145243.5(OMA1):​c.632T>G​(p.Phe211Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0225 in 872,832 control chromosomes in the GnomAD database, including 565 homozygotes. In-silico tool predicts 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 0.018 (57 hom., cov: 32)
  • Exomes 𝑓: 0.023 (508 hom.)
• Consequence: OMA1 NM_145243.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.64

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002847284).
• BP6: Variant 1-58536610-A-C is Benign according to our data. Variant chr1-58536610-A-C is described in ClinVar as [Benign]. Clinvar id is 1287065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5	c.632T>G	p.Phe211Cys	missense_variant	3/9	ENST00000371226.8
DAB1	NM_001379461.1	c.-729-9275T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8	c.632T>G	p.Phe211Cys	missense_variant	3/9	1	NM_145243.5	P1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2816 AN: 152172 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0590

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0265 AC: 6665 AN: 251320 Hom.: 228 AF XY: 0.0279 AC XY: 3794 AN XY: 135832

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.0555

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.0133

Gnomad OTH exome AF: 0.0220

GnomAD4 exome AF: 0.0234 AC: 16829 AN: 720542 Hom.: 508 Cov.: 0 AF XY: 0.0248 AC XY: 9556 AN XY: 384630

Gnomad4 AFR exome AF: 0.00790

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.0542

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0185 AC: 2813 AN: 152290 Hom.: 57 Cov.: 32 AF XY: 0.0198 AC XY: 1478 AN XY: 74468

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0588

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0165 Hom.: 97

Bravo AF: 0.0176

TwinsUK AF: 0.0119 AC: 44

ALSPAC AF: 0.0148 AC: 57

ESP6500AA AF: 0.00976 AC: 43

ESP6500EA AF: 0.0121 AC: 104

ExAC AF: 0.0262 AC: 3183

Asia WGS AF: 0.0800 AC: 278 AN: 3476

EpiCase AF: 0.0124

EpiControl AF: 0.0133

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 32236861) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;T;T;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T;T
MetaRNN	Benign	0.0028	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.;.
MutationTaster	Benign	0.000027	P;P
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.9	D;D;D;D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0080	D;.;.;.
Polyphen		1.0	D;.;.;.
Vest4		0.24
MPC		0.44
ClinPred		0.021	T
GERP RS		5.5
Varity_R		0.47
gMVP		0.52

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

Other links and lift over

dbSNP: rs17117699; hg19: chr1-59002282; COSMIC: COSV62257245; COSMIC: COSV62257245;