Variant 19-13764950-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001031727.4(MRI1):c.212G>A(p.Gly71Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000982 in 1,507,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

MRI1
NM_001031727.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Variant links:

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]

MRI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04420826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRI1	NM_001031727.4 linkuse as main transcript	c.212G>A	p.Gly71Glu	missense_variant	2/6	ENST00000040663.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRI1	ENST00000040663.8 linkuse as main transcript	c.212G>A	p.Gly71Glu	missense_variant	2/6	1	NM_001031727.4	P1	Q9BV20-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000171

AC:

AN:

111288

Hom.:

AF XY:

0.000195

AC XY:

AN XY:

61696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000927

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000254

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000685

Gnomad OTH exome

AF:

0.000289

GnomAD4 exome

AF:

0.0000944

AC:

128

AN:

1355358

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

667516

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000149

Gnomad4 ASJ exome

AF:

0.000619

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000732

Gnomad4 OTH exome

AF:

0.000141

GnomAD4 genome

AF:

0.000132

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000908

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.212G>A (p.G71E) alteration is located in exon 2 (coding exon 2) of the MRI1 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the glycine (G) at amino acid position 71 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Benign

0.78

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.78

T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.044

T;T

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.24

N;N

MutationTaster

Benign

0.61

D;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.26

Sift

Benign

0.60

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.98

D;B

Vest4

0.55

MutPred

0.37

Gain of stability (P = 0.0417);Gain of stability (P = 0.0417);

MVP

0.60

MPC

0.31

ClinPred

0.075

GERP RS

4.4

Varity_R

0.12

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over