chr1-58539094-G-T

Position:

• chr1-58539094-G-T

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.201C>A​(p.Asn67Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00791 in 872,778 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.028 (190 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (110 hom.)
• Consequence: OMA1 NM_145243.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.42

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=0.0020210743).
• BP6: Variant 1-58539094-G-T is Benign according to our data. Variant chr1-58539094-G-T is described in ClinVar as [Benign]. Clinvar id is 780242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OMA1	NM_145243.5	c.201C>A	p.Asn67Lys	missense_variant	2/9	ENST00000371226.8
DAB1	NM_001379461.1	c.-730+7609C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OMA1	ENST00000371226.8	c.201C>A	p.Asn67Lys	missense_variant	2/9	1	NM_145243.5	P1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4254 AN: 152040 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.00723 AC: 1815 AN: 251162 Hom.: 74 AF XY: 0.00501 AC XY: 681 AN XY: 135806

Gnomad AFR exome AF: 0.0992

Gnomad AMR exome AF: 0.00411

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: 0.00458

GnomAD4 exome AF: 0.00366 AC: 2639 AN: 720620 Hom.: 110 Cov.: 0 AF XY: 0.00301 AC XY: 1158 AN XY: 384658

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00504

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000363

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00644

GnomAD4 genome AF: 0.0280 AC: 4266 AN: 152158 Hom.: 190 Cov.: 32 AF XY: 0.0273 AC XY: 2032 AN XY: 74418

Gnomad4 AFR AF: 0.0965

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.00494 Hom.: 41

Bravo AF: 0.0317

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0931 AC: 410

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00906 AC: 1100

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000593

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	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T;T;T;.;.
Eigen	Benign	0.033
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.68	T;T;T;T;T;T
MetaRNN	Benign	0.0020	T;T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.;.
MutationTaster	Benign	0.90	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	N;N;N;N;N;.
REVEL	Benign	0.028
Sift	Benign	0.033	D;D;D;D;D;.
Sift4G	Benign	0.082	T;.;.;.;.;.
Polyphen		0.80	P;.;.;.;.;.
Vest4		0.38
MutPred		0.25		Gain of methylation at N67 (P = 0.0053);Gain of methylation at N67 (P = 0.0053);Gain of methylation at N67 (P = 0.0053);Gain of methylation at N67 (P = 0.0053);Gain of methylation at N67 (P = 0.0053);Gain of methylation at N67 (P = 0.0053);
MVP		0.28
MPC		0.21
ClinPred		0.020	T
GERP RS		4.5
Varity_R		0.047
gMVP		0.32

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: rs34466938; hg19: chr1-59004766;