chr1-58534306-A-G
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_145243.5(OMA1):āc.755T>Cā(p.Met252Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 856,292 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 (ā ā ).
Frequency
Genomes: š 0.00064 ( 1 hom., cov: 33)
Exomes š: 0.0010 ( 10 hom. )
Consequence
OMA1
NM_145243.5 missense
NM_145243.5 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.46
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009375572).
BP6
Variant 1-58534306-A-G is Benign according to our data. Variant chr1-58534306-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 729080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 10 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OMA1 | NM_145243.5 | c.755T>C | p.Met252Thr | missense_variant | 4/9 | ENST00000371226.8 | NP_660286.1 | |
DAB1 | NM_001379461.1 | c.-729-6971T>C | intron_variant | NP_001366390.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OMA1 | ENST00000371226.8 | c.755T>C | p.Met252Thr | missense_variant | 4/9 | 1 | NM_145243.5 | ENSP00000360270.3 |
Frequencies
GnomAD3 genomes AF: 0.000644 AC: 98AN: 152200Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00111 AC: 259AN: 233936Hom.: 4 AF XY: 0.00130 AC XY: 165AN XY: 126456
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GnomAD4 exome AF: 0.00102 AC: 715AN: 703974Hom.: 10 Cov.: 0 AF XY: 0.00127 AC XY: 478AN XY: 375504
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GnomAD4 genome AF: 0.000643 AC: 98AN: 152318Hom.: 1 Cov.: 33 AF XY: 0.000752 AC XY: 56AN XY: 74480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 20, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;.;.;.
Polyphen
P;.;.;.
Vest4
MVP
MPC
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T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at