1-236795711-CCG-C
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000254.3(MTR):c.12_13delGC(p.Leu5ProfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
MTR
NM_000254.3 frameshift
NM_000254.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.01
Publications
1 publications found
Genes affected
MTR (HGNC:7468): (5-methyltetrahydrofolate-homocysteine methyltransferase) This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
MTR Gene-Disease associations (from GenCC):
- methylcobalamin deficiency type cblGInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 71 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-236795711-CCG-C is Pathogenic according to our data. Variant chr1-236795711-CCG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 2769519.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000254.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MTR | MANE Select | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 33 | NP_000245.2 | Q99707-1 | ||
| MTR | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 32 | NP_001278868.1 | Q99707-2 | |||
| MTR | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 31 | NP_001397871.1 | A0A7P0TAJ0 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTR | TSL:1 MANE Select | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 33 | ENSP00000355536.5 | Q99707-1 | ||
| MTR | TSL:1 | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 32 | ENSP00000441845.1 | Q99707-2 | ||
| MTR | c.12_13delGC | p.Leu5ProfsTer16 | frameshift | Exon 1 of 32 | ENSP00000505600.1 | A0A7P0T9G7 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251188 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251188
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461798Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727208 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461798
Hom.:
AF XY:
AC XY:
2
AN XY:
727208
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53334
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1112002
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Methylcobalamin deficiency type cblG (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
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