chr2-149575863-C-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015702.3(MMADHC):c.479-22G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,553,354 control chromosomes in the GnomAD database, including 458,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.65 ( 35624 hom., cov: 33)
Exomes 𝑓: 0.77 ( 422844 hom. )
Consequence
MMADHC
NM_015702.3 intron
NM_015702.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.14
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 Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 2-149575863-C-G is Benign according to our data. Variant chr2-149575863-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 260678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMADHC | NM_015702.3 | c.479-22G>C | intron_variant | ENST00000303319.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMADHC | ENST00000303319.10 | c.479-22G>C | intron_variant | 1 | NM_015702.3 | P1 | |||
MMADHC | ENST00000422782.2 | c.479-22G>C | intron_variant | 5 | |||||
MMADHC | ENST00000428879.5 | c.479-22G>C | intron_variant | 2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.649 AC: 98502AN: 151850Hom.: 35618 Cov.: 33
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GnomAD3 exomes AF: 0.751 AC: 168708AN: 224514Hom.: 65139 AF XY: 0.759 AC XY: 92148AN XY: 121354
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GnomAD4 exome AF: 0.772 AC: 1081754AN: 1401388Hom.: 422844 Cov.: 24 AF XY: 0.773 AC XY: 539225AN XY: 697548
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GnomAD4 genome AF: 0.648 AC: 98521AN: 151966Hom.: 35624 Cov.: 33 AF XY: 0.653 AC XY: 48479AN XY: 74274
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | - - |
Methylmalonic aciduria and homocystinuria type cblD Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at