19-13765090-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001031727.4(MRI1):c.352G>A(p.Glu118Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,540,396 control chromosomes in the GnomAD database, including 4 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (4 hom.)
• Consequence: MRI1 NM_001031727.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.38

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006574005).
• BP6: Variant 19-13765090-G-A is Benign according to our data. Variant chr19-13765090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718651.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRI1	NM_001031727.4	c.352G>A	p.Glu118Lys	missense_variant	2/6	ENST00000040663.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRI1	ENST00000040663.8	c.352G>A	p.Glu118Lys	missense_variant	2/6	1	NM_001031727.4	P1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152242 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00105 AC: 171 AN: 162836 Hom.: 0 AF XY: 0.00113 AC XY: 101 AN XY: 89364

Gnomad AFR exome AF: 0.000572

Gnomad AMR exome AF: 0.000794

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000613

Gnomad FIN exome AF: 0.000395

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.000480

GnomAD4 exome AF: 0.00224 AC: 3111 AN: 1388036 Hom.: 4 Cov.: 32 AF XY: 0.00216 AC XY: 1484 AN XY: 687222

Gnomad4 AFR exome AF: 0.000527

Gnomad4 AMR exome AF: 0.000865

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000286

Gnomad4 SAS exome AF: 0.000724

Gnomad4 FIN exome AF: 0.000353

Gnomad4 NFE exome AF: 0.00267

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152360 Hom.: 0 Cov.: 31 AF XY: 0.00130 AC XY: 97 AN XY: 74500

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00240

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00161

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00244 AC: 20

ExAC AF: 0.000884 AC: 105

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	21
Dann	Benign	0.82
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.0066	T;T
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.54	N;N
REVEL	Uncertain	0.33
Sift	Benign	0.73	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.21	B;B
Vest4		0.44
MVP		0.74
MPC		0.31
ClinPred		0.017	T
GERP RS		5.3
Varity_R		0.18
gMVP		0.51

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

Other links and lift over

dbSNP: rs200063247; hg19: chr19-13875904;