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rs397509362

chr2-149579478-T-TTGATAAAGGTTCTGCTAG

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

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: 1.45
Variant links:
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
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Nonframeshift variant in NON repetitive region in NM_015702.3.
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
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 UniProt
MMADHCNM_015702.3 linkuse as main transcriptc.324_325insCTAGCAGAACCTTTATCA p.Leu103_Ser108dup inframe_insertion 4/8 ENST00000303319.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MMADHCENST00000303319.10 linkuse as main transcriptc.324_325insCTAGCAGAACCTTTATCA p.Leu103_Ser108dup inframe_insertion 4/81 NM_015702.3 P1
MMADHCENST00000422782.2 linkuse as main transcriptc.324_325insCTAGCAGAACCTTTATCA p.Leu103_Ser108dup inframe_insertion 4/95
MMADHCENST00000428879.5 linkuse as main transcriptc.324_325insCTAGCAGAACCTTTATCA p.Leu103_Ser108dup inframe_insertion 3/72 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Vitamin B12-responsive methylmalonic acidemia, type cblDv2 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 03, 2008- -
Methylmalonic aciduria and homocystinuria type cblD Other:1
not provided, no classification providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs397509362; hg19: chr2-150435992; API