chr12-4659027-A-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005002.5(NDUFA9):c.411-9A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,606,668 control chromosomes in the GnomAD database, including 55,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.26 ( 5230 hom., cov: 33)
Exomes 𝑓: 0.26 ( 50056 hom. )
Consequence
NDUFA9
NM_005002.5 splice_polypyrimidine_tract, intron
NM_005002.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001367
2
Clinical Significance
Conservation
PhyloP100: 2.11
Genes affected
NDUFA9 (HGNC:7693): (NADH:ubiquinone oxidoreductase subunit A9) The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex I), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane. A pseudogene has been identified on chromosome 12. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 12-4659027-A-T is Benign according to our data. Variant chr12-4659027-A-T is described in ClinVar as [Benign]. Clinvar id is 138447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-4659027-A-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFA9 | NM_005002.5 | c.411-9A>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000266544.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFA9 | ENST00000266544.10 | c.411-9A>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005002.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.259 AC: 39322AN: 151980Hom.: 5236 Cov.: 33
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GnomAD3 exomes AF: 0.244 AC: 60822AN: 249372Hom.: 7783 AF XY: 0.244 AC XY: 32903AN XY: 135038
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GnomAD4 exome AF: 0.258 AC: 375233AN: 1454570Hom.: 50056 Cov.: 31 AF XY: 0.257 AC XY: 186110AN XY: 723828
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GnomAD4 genome ? AF: 0.259 AC: 39321AN: 152098Hom.: 5230 Cov.: 33 AF XY: 0.252 AC XY: 18711AN XY: 74350
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Feb 22, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at