rs141094096
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001031727.4(MRI1):c.629G>A(p.Arg210Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000998 in 1,613,778 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00010 ( 1 hom. )
Consequence
MRI1
NM_001031727.4 missense
NM_001031727.4 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 8.94
Genes affected
MRI1 (HGNC:28469): (methylthioribose-1-phosphate isomerase 1) This enzyme functions in the methionine salvage pathway by catalyzing the interconversion of methylthioribose-1-phosphate and methythioribulose-1-phosphate. Elevated expression of the encoded protein is associated with metastatic melanoma and this protein promotes melanoma cell invasion independent of its enzymatic activity. Mutations in this gene may be associated with vanishing white matter disease (VMWD). [provided by RefSeq, Jul 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.794
PP5
?
Variant 19-13768642-G-A is Pathogenic according to our data. Variant chr19-13768642-G-A is described in ClinVar as [Uncertain_significance]. Clinvar id is 183306.Status of the report is criteria_provided_single_submitter, 1 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=1}. Variant chr19-13768642-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRI1 | NM_001031727.4 | c.629G>A | p.Arg210Gln | missense_variant | 4/6 | ENST00000040663.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRI1 | ENST00000040663.8 | c.629G>A | p.Arg210Gln | missense_variant | 4/6 | 1 | NM_001031727.4 | P1 | |
MRI1 | ENST00000319545.12 | c.488G>A | p.Arg163Gln | missense_variant | 4/6 | 1 | |||
MRI1 | ENST00000588526.5 | n.824G>A | non_coding_transcript_exon_variant | 4/4 | 2 | ||||
MRI1 | ENST00000591688.5 | n.669G>A | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152208Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
14
AN:
152208
Hom.:
Cov.:
31
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: 0.000132 AC: 33AN: 249662Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135352
GnomAD3 exomes
AF:
AC:
33
AN:
249662
Hom.:
AF XY:
AC XY:
19
AN XY:
135352
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: 0.000101 AC: 147AN: 1461452Hom.: 1 Cov.: 31 AF XY: 0.000116 AC XY: 84AN XY: 727048
GnomAD4 exome
AF:
AC:
147
AN:
1461452
Hom.:
Cov.:
31
AF XY:
AC XY:
84
AN XY:
727048
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:
GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152326Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74488
GnomAD4 genome
?
AF:
AC:
14
AN:
152326
Hom.:
Cov.:
31
AF XY:
AC XY:
9
AN XY:
74488
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
17
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Severe cystic degeneration of the brain;CN228296:Infantile epilepsy Pathogenic:1
Likely pathogenic, flagged submission | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Dec 01, 2014 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.93
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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