4-145639175-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_172250.3(MMAA):c.36C>T(p.Phe12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
MMAA
NM_172250.3 synonymous
NM_172250.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.18
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 Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 4-145639175-C-T is Benign according to our data. Variant chr4-145639175-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1158925.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.18 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MMAA | NM_172250.3 | c.36C>T | p.Phe12= | synonymous_variant | 2/7 | ENST00000649156.2 | |
MMAA | NM_001375644.1 | c.36C>T | p.Phe12= | synonymous_variant | 2/7 | ||
MMAA | XM_011531684.4 | c.36C>T | p.Phe12= | synonymous_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MMAA | ENST00000649156.2 | c.36C>T | p.Phe12= | synonymous_variant | 2/7 | NM_172250.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727232
GnomAD4 exome
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AC:
1
AN:
1461870
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Cov.:
32
AF XY:
AC XY:
1
AN XY:
727232
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Methylmalonic aciduria, cblA type Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at