chr4-145639126-C-T
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_172250.3(MMAA):c.-14C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,613,862 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 5 hom. )
Consequence
MMAA
NM_172250.3 5_prime_UTR
NM_172250.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.455
Genes affected
MMAA (HGNC:18871): (metabolism of cobalamin associated A) The protein encoded by this gene is involved in the translocation of cobalamin into the mitochondrion, where it is used in the final steps of adenosylcobalamin synthesis. Adenosylcobalamin is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this gene are a cause of methylmalonic aciduria. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 4-145639126-C-T is Benign according to our data. Variant chr4-145639126-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 902093.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00158 (240/152288) while in subpopulation NFE AF= 0.00256 (174/68008). AF 95% confidence interval is 0.00225. There are 1 homozygotes in gnomad4. There are 116 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAA | NM_172250.3 | c.-14C>T | 5_prime_UTR_variant | 2/7 | ENST00000649156.2 | ||
MMAA | NM_001375644.1 | c.-14C>T | 5_prime_UTR_variant | 2/7 | |||
MMAA | XM_011531684.4 | c.-14C>T | 5_prime_UTR_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAA | ENST00000649156.2 | c.-14C>T | 5_prime_UTR_variant | 2/7 | NM_172250.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00158 AC: 240AN: 152170Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00154 AC: 386AN: 251258Hom.: 2 AF XY: 0.00146 AC XY: 198AN XY: 135824
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GnomAD4 exome AF: 0.00233 AC: 3409AN: 1461574Hom.: 5 Cov.: 31 AF XY: 0.00231 AC XY: 1681AN XY: 727118
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GnomAD4 genome AF: 0.00158 AC: 240AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblA type Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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