chr4-145639175-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_172250.3(MMAA):c.36C>T(p.Phe12Phe) 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
Publications
0 publications found
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]
MMAA Gene-Disease associations (from GenCC):
- methylmalonic aciduria, cblA typeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, ClinGen, Ambry Genetics, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -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 VariationId is 1158925.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.18 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_172250.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MMAA | NM_172250.3 | MANE Select | c.36C>T | p.Phe12Phe | synonymous | Exon 2 of 7 | NP_758454.1 | Q8IVH4 | |
| MMAA | NM_001375644.1 | c.36C>T | p.Phe12Phe | synonymous | Exon 2 of 7 | NP_001362573.1 | Q8IVH4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MMAA | ENST00000649156.2 | MANE Select | c.36C>T | p.Phe12Phe | synonymous | Exon 2 of 7 | ENSP00000497008.1 | Q8IVH4 | |
| MMAA | ENST00000511969.4 | TSL:1 | n.36C>T | non_coding_transcript_exon | Exon 1 of 5 | ENSP00000427422.1 | D6RIS5 | ||
| MMAA | ENST00000541599.5 | TSL:5 | c.36C>T | p.Phe12Phe | synonymous | Exon 2 of 7 | ENSP00000442284.3 | Q8IVH4 |
Frequencies
GnomAD3 genomes
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 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461870
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727232
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1112006
Other (OTH)
AF:
AC:
0
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
1
Methylmalonic aciduria, cblA type (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.