NM_000255.4:c.1038_1040delTCT
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong
The NM_000255.4(MMUT):c.1038_1040delTCT(p.Leu347del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_000255.4 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MMUT | NM_000255.4 | c.1038_1040delTCT | p.Leu347del | disruptive_inframe_deletion | Exon 5 of 13 | ENST00000274813.4 | NP_000246.2 | |
MMUT | XM_005249143.4 | c.1038_1040delTCT | p.Leu347del | disruptive_inframe_deletion | Exon 5 of 13 | XP_005249200.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251228Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135792
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460784Hom.: 0 AF XY: 0.00000550 AC XY: 4AN XY: 726770
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152096Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency Pathogenic:3
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not provided Pathogenic:1
This variant, c.1038_1040del, results in the deletion of 1 amino acid(s) of the MUT protein (p.Leu347del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs765373403, gnomAD 0.006%). This variant has been observed in individual(s) with methylmalonic acidemia (PMID: 15643616, 15781192, 16281286, 26790480). This variant is also known as c.1036-1038delCTT, p.L346del. ClinVar contains an entry for this variant (Variation ID: 225184). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic. -
Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at