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GeneBe

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 (β˜…β˜…).

Frequency

Genomes: 𝑓 0.45 ( 16801 hom., cov: 34)
Exomes 𝑓: 0.47 ( 29891 hom. )

Consequence

MTRR
NM_002454 missense

Scores

7
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:9O:2

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
MTRRNM_002454.3 linkuse as main transcriptc.66A>G p.Ile22Met missense_variant 2/15 ENST00000440940.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTRRENST00000440940.7 linkuse as main transcriptc.66A>G p.Ile22Met missense_variant 2/151 NM_002454.3 P1Q9UBK8-2

Frequencies

GnomAD3 genomes
AF:
0.451
AC:
68524
AN:
152052
Hom.:
16801
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.281
Gnomad AMI
AF:
0.676
Gnomad AMR
AF:
0.367
Gnomad ASJ
AF:
0.456
Gnomad EAS
AF:
0.283
Gnomad SAS
AF:
0.529
Gnomad FIN
AF:
0.578
Gnomad MID
AF:
0.385
Gnomad NFE
AF:
0.558
Gnomad OTH
AF:
0.430
GnomAD3 exomes
AF:
0.466
AC:
117132
AN:
251460
Hom.:
29891
AF XY:
0.482
AC XY:
65443
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.274
Gnomad AMR exome
AF:
0.250
Gnomad ASJ exome
AF:
0.455
Gnomad EAS exome
AF:
0.279
Gnomad SAS exome
AF:
0.525
Gnomad FIN exome
AF:
0.565
Gnomad NFE exome
AF:
0.554
Gnomad OTH exome
AF:
0.491
GnomAD4 exome
AF:
0.532
AC:
777894
AN:
1461798
Hom.:
212709
AF XY:
0.534
AC XY:
387990
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.275
Gnomad4 AMR exome
AF:
0.264
Gnomad4 ASJ exome
AF:
0.448
Gnomad4 EAS exome
AF:
0.292
Gnomad4 SAS exome
AF:
0.524
Gnomad4 FIN exome
AF:
0.572
Gnomad4 NFE exome
AF:
0.562
Gnomad4 OTH exome
AF:
0.500
Alfa
AF:
0.515
Hom.:
43514
Bravo
AF:
0.421
TwinsUK
AF:
0.553
AC:
2050
ALSPAC
AF:
0.565
AC:
2179
ESP6500AA
AF:
0.270
AC:
1188
ESP6500EA
AF:
0.546
AC:
4696
ExAC
AF:
0.473
AC:
57411
Asia WGS
AF:
0.387
AC:
1347
AN:
3478
EpiCase
AF:
0.529
EpiControl
AF:
0.524

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 submitterclinical testingPreventionGenetics, PreventionGenetics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 26, 2013This 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 providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Methylcobalamin deficiency type cblE Benign:4
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Benign, criteria provided, single submitterclinical testingInvitaeNov 04, 2022- -
Benign, criteria provided, single submitterclinical testingPars Genome LabJun 19, 2021- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, no assertion criteria providedcase-controlDepartment of Pharmacy and Biotechnology, University of Bologna-- -
Disorders of Intracellular Cobalamin Metabolism Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This 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 providedliterature onlyOMIMJul 01, 2005- -
Neural tube defects, folate-sensitive, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJul 01, 2005- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.090
Cadd
Benign
23
Dann
Uncertain
0.99
Eigen
Benign
-0.070
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.10
N
LIST_S2
Uncertain
0.92
D;D;D;D;D
MetaRNN
Benign
0.00045
T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.3
M;.;.;.;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-2.2
N;N;D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0020
D;D;D;T;D
Sift4G
Uncertain
0.0070
D;D;D;D;D
Vest4
0.26
MPC
0.32
ClinPred
0.049
T
GERP RS
0.33
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.37
gMVP
0.77

Splicing

Find out SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1801394; hg19: chr5-7870973; COSMIC: COSV52943975; COSMIC: COSV52943975;