chr12-94971477-ATCT-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBS1_SupportingBS2
The NM_018838.5(NDUFA12):c.398_400delAGA(p.Lys133del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00146 in 1,614,170 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_018838.5 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00101 AC: 153AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000808 AC: 203AN: 251354Hom.: 0 AF XY: 0.000861 AC XY: 117AN XY: 135846
GnomAD4 exome AF: 0.00150 AC: 2200AN: 1461866Hom.: 4 AF XY: 0.00148 AC XY: 1075AN XY: 727238
GnomAD4 genome AF: 0.00100 AC: 153AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:3
This variant, c.398_400del, results in the deletion of 1 amino acid(s) of the NDUFA12 protein (p.Lys133del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs561604238, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NDUFA12-related conditions. ClinVar contains an entry for this variant (Variation ID: 806925). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
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In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Inborn genetic diseases Benign:1
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