chr4-145639105-A-T
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_172250.3(MMAA):c.-35A>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 0.000622 in 1,602,752 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0033 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 1 hom. )
Consequence
MMAA
NM_172250.3 5_prime_UTR
NM_172250.3 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.07
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 -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 4-145639105-A-T is Benign according to our data. Variant chr4-145639105-A-T is described in ClinVar as [Benign]. Clinvar id is 383060.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00331 (505/152358) while in subpopulation AFR AF= 0.0114 (476/41584). AF 95% confidence interval is 0.0106. There are 3 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAA | NM_172250.3 | c.-35A>T | 5_prime_UTR_variant | 2/7 | ENST00000649156.2 | ||
MMAA | NM_001375644.1 | c.-35A>T | 5_prime_UTR_variant | 2/7 | |||
MMAA | XM_011531684.4 | c.-35A>T | 5_prime_UTR_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAA | ENST00000649156.2 | c.-35A>T | 5_prime_UTR_variant | 2/7 | NM_172250.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00332 AC: 506AN: 152240Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000945 AC: 237AN: 250884Hom.: 2 AF XY: 0.000553 AC XY: 75AN XY: 135722
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GnomAD4 exome AF: 0.000339 AC: 492AN: 1450394Hom.: 1 Cov.: 29 AF XY: 0.000258 AC XY: 186AN XY: 722242
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GnomAD4 genome AF: 0.00331 AC: 505AN: 152358Hom.: 3 Cov.: 32 AF XY: 0.00317 AC XY: 236AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Benign
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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