rs746483754
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_000016.6(ACADM):c.709-13A>G 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 0.000011 in 1,460,902 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).
Frequency
Consequence
NM_000016.6 splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACADM | NM_000016.6 | c.709-13A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000370841.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACADM | ENST00000370841.9 | c.709-13A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000016.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250266Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135592
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460902Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 726718
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Medium-chain acyl-coenzyme A dehydrogenase deficiency Pathogenic:2Uncertain:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 23, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | This sequence change falls in intron 8 of the ACADM gene. It does not directly change the encoded amino acid sequence of the ACADM protein. This variant is present in population databases (rs746483754, gnomAD 0.007%). This variant has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 20434380, 21083904; Invitae). This variant is also known as IVS8-13A>G. ClinVar contains an entry for this variant (Variation ID: 198979). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Sep 27, 2017 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 01, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 18, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at