rs1801394
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002454(MTRR):c.66A>G(p.Ile22Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152052 control chromosomes in the gnomAD Genomes database, including 16801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (โ โ ).
Frequency
Genomes: ๐ 0.45 ( 16801 hom., cov: 34)
Exomes ๐: 0.47 ( 29891 hom. )
Consequence
MTRR
NM_002454 missense
NM_002454 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 0.0980
Links
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=4.4935942E-4).
BP6
?
Variant 5:7870860-A>G is Benign according to our data. Variant chr5-7870860-A-G is described in ClinVar as [Benign]. Clinvar id is 7029. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-7870860-A-G is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTRR | NM_002454.3 | c.66A>G | p.Ile22Met | missense_variant | 2/15 | ENST00000440940.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTRR | ENST00000440940.7 | c.66A>G | p.Ile22Met | missense_variant | 2/15 | 1 | NM_002454.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.451 AC: 68524AN: 152052Hom.: 16801 Cov.: 34
GnomAD3 genomes
AF:
AC:
68524
AN:
152052
Hom.:
Cov.:
34
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.466 AC: 117132AN: 251460Hom.: 29891 AF XY: 0.482 AC XY: 65443AN XY: 135902
GnomAD3 exomes
AF:
AC:
117132
AN:
251460
Hom.:
AF XY:
AC XY:
65443
AN XY:
135902
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.532 AC: 777894AN: 1461798Hom.: 212709 AF XY: 0.534 AC XY: 387990AN XY: 727196
GnomAD4 exome
AF:
AC:
777894
AN:
1461798
Hom.:
AF XY:
AC XY:
387990
AN XY:
727196
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
2050
ALSPAC
AF:
AC:
2179
ESP6500AA
AF:
AC:
1188
ESP6500EA
AF:
AC:
4696
ExAC
AF:
AC:
57411
Asia WGS
AF:
AC:
1347
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:9Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, PreventionGenetics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 26, 2013 | 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. - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Methylcobalamin deficiency type cblE Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 04, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, no assertion criteria provided | case-control | Department of Pharmacy and Biotechnology, University of Bologna | - | - - |
Disorders of Intracellular Cobalamin Metabolism Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Down syndrome, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jul 01, 2005 | - - |
Neural tube defects, folate-sensitive, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Jul 01, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
P;P;P
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;T;D
Sift4G
Uncertain
D;D;D;D;D
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Find out SpliceAI and Pangolin per-transcript scores at