1-39084253-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_012090.5(MACF1):c.35G>A(p.Arg12Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,612,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12W) has been classified as Likely benign.
Frequency
Consequence
NM_012090.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MACF1 | ENST00000567887.5 | c.35G>A | p.Arg12Gln | missense_variant | Exon 1 of 101 | 5 | ENSP00000455823.1 | |||
MACF1 | ENST00000372915.8 | c.35G>A | p.Arg12Gln | missense_variant | Exon 1 of 96 | 5 | ENSP00000362006.4 | |||
MACF1 | ENST00000361689.7 | c.35G>A | p.Arg12Gln | missense_variant | Exon 2 of 94 | 5 | ENSP00000354573.2 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251092Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135762
GnomAD4 exome AF: 0.000242 AC: 354AN: 1460536Hom.: 0 Cov.: 30 AF XY: 0.000208 AC XY: 151AN XY: 726652
GnomAD4 genome AF: 0.000145 AC: 22AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74334
ClinVar
Submissions by phenotype
Lissencephaly 9 with complex brainstem malformation Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 28, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at