3-128910014-ATCCCAGACCATC-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate
The NM_014049.5(ACAD9):c.1564-6_1569delTCCCAGACCATC(p.Thr522_Met524del) variant causes a splice acceptor, conservative inframe deletion, splice region, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_014049.5 splice_acceptor, conservative_inframe_deletion, splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CFAP92 | NM_001394090.1 | c.*273_*284delGATGGTCTGGGA | 3_prime_UTR_variant | Exon 16 of 16 | ENST00000645291.3 | NP_001381019.1 | ||
ACAD9 | NM_014049.5 | c.1564-6_1569delTCCCAGACCATC | p.Thr522_Met524del | splice_acceptor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant | Exon 16 of 18 | ENST00000308982.12 | NP_054768.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CFAP92 | ENST00000645291 | c.*273_*284delGATGGTCTGGGA | 3_prime_UTR_variant | Exon 16 of 16 | NM_001394090.1 | ENSP00000496592.2 | ||||
ACAD9 | ENST00000308982.12 | c.1564-6_1569delTCCCAGACCATC | p.Thr522_Met524del | splice_acceptor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant | Exon 16 of 18 | 1 | NM_014049.5 | ENSP00000312618.7 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
This variant results in the deletion of part of exon 16 (c.1564-6_1569del) of the ACAD9 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACAD9 are known to be pathogenic (PMID: 25721401). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 242460). This variant has been observed in individual(s) with clinical features of mitochondrial complex I deficiency (PMID: 26669660, 30025539). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at