rs397509362
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_015702.3(MMADHC):c.324_325insCTAGCAGAACCTTTATCA(p.Leu103_Ser108dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
MMADHC
NM_015702.3 inframe_insertion
NM_015702.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.45
Genes affected
MMADHC (HGNC:25221): (metabolism of cobalamin associated D) This gene encodes a mitochondrial protein that is involved in an early step of vitamin B12 metabolism. Vitamin B12 (cobalamin) is essential for normal development and survival in humans. Mutations in this gene cause methylmalonic aciduria and homocystinuria type cblD (MMADHC), a disorder of cobalamin metabolism that is characterized by decreased levels of the coenzymes adenosylcobalamin and methylcobalamin. Pseudogenes have been identified on chromosomes 11 and X.[provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_015702.3.
PP5
Variant 2-149579478-T-TTGATAAAGGTTCTGCTAG is Pathogenic according to our data. Variant chr2-149579478-T-TTGATAAAGGTTCTGCTAG is described in ClinVar as [Pathogenic]. Clinvar id is 766.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MMADHC | NM_015702.3 | c.324_325insCTAGCAGAACCTTTATCA | p.Leu103_Ser108dup | inframe_insertion | 4/8 | ENST00000303319.10 | NP_056517.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MMADHC | ENST00000303319.10 | c.324_325insCTAGCAGAACCTTTATCA | p.Leu103_Ser108dup | inframe_insertion | 4/8 | 1 | NM_015702.3 | ENSP00000301920 | P1 | |
| MMADHC | ENST00000422782.2 | c.324_325insCTAGCAGAACCTTTATCA | p.Leu103_Ser108dup | inframe_insertion | 4/9 | 5 | ENSP00000408331 | |||
| MMADHC | ENST00000428879.5 | c.324_325insCTAGCAGAACCTTTATCA | p.Leu103_Ser108dup | inframe_insertion | 3/7 | 2 | ENSP00000389060 | P1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
METHYLMALONIC ACIDURIA, cblD TYPE Pathogenic:1
| Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 03, 2008 | - - |
Methylmalonic aciduria and homocystinuria type cblD Other:1
| not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at