chr16-83899157-GGGCCAGGCTTGAC-G
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_012213.3(MLYCD):c.22_34delTTGACGGCCAGGC(p.Leu8ValfsTer61) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,148,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_012213.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MLYCD | ENST00000262430.6 | c.22_34delTTGACGGCCAGGC | p.Leu8ValfsTer61 | frameshift_variant | Exon 1 of 5 | 1 | NM_012213.3 | ENSP00000262430.4 | ||
ENSG00000288849 | ENST00000689373.1 | n.1202-7821_1202-7809delTTGACGGCCAGGC | intron_variant | Intron 5 of 8 | ||||||
ENSG00000288849 | ENST00000692462.1 | n.1170-7821_1170-7809delTTGACGGCCAGGC | intron_variant | Intron 5 of 8 |
Frequencies
GnomAD3 genomes AF: 0.00000668 AC: 1AN: 149660Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000400 AC: 4AN: 999224Hom.: 0 AF XY: 0.00000419 AC XY: 2AN XY: 477508
GnomAD4 genome AF: 0.00000668 AC: 1AN: 149660Hom.: 0 Cov.: 33 AF XY: 0.0000137 AC XY: 1AN XY: 72998
ClinVar
Submissions by phenotype
Deficiency of malonyl-CoA decarboxylase Pathogenic:1
This variant has not been reported in the literature in individuals affected with MLYCD-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu8Valfs*61) in the MLYCD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLYCD are known to be pathogenic (PMID: 12955715, 17186413). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at