Variant 1-181049117-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000367580.6(MR1):c.133A>G(p.Ile45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MR1
ENST00000367580.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.509

Variant links:

Genes affected

MR1 (HGNC:4975): (major histocompatibility complex, class I-related) MAIT (mucosal-associated invariant T-cells) lymphocytes represent a small population of T-cells primarily found in the gut. The protein encoded by this gene is an antigen-presenting molecule that presents metabolites of microbial vitamin B to MAITs. This presentation may activate the MAITs to regulate the amounts of specific types of bacteria in the gut. Several transcript variants encoding different isoforms have been found for this gene, and a pseudogene of it has been detected about 36 kbp upstream on the same chromosome. [provided by RefSeq, Jul 2015]

MR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083425075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MR1	NM_001385161.1 linkuse as main transcript	c.133A>G	p.Ile45Val	missense_variant	2/6	ENST00000367580.6	NP_001372090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MR1	ENST00000367580.6 linkuse as main transcript	c.133A>G	p.Ile45Val	missense_variant	2/6	1	NM_001385161.1	ENSP00000356552	P1	Q95460-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 21, 2024

The c.133A>G (p.I45V) alteration is located in exon 3 (coding exon 2) of the MR1 gene. This alteration results from a A to G substitution at nucleotide position 133, causing the isoleucine (I) at amino acid position 45 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

2.4

DANN

Benign

0.86

DEOGEN2

Benign

0.050

.;T;.;.;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.80

T;T;T;T;.;.

M_CAP

Benign

0.0022

MetaRNN

Benign

0.083

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.78

N;N;N;N;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.26

.;.;N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.59

.;.;T;D;T;T

Sift4G

Benign

0.24

T;T;T;T;T;T

Polyphen

0.53

P;P;.;P;P;P

Vest4

0.051

MutPred

0.63

Gain of phosphorylation at Y49 (P = 0.105);Gain of phosphorylation at Y49 (P = 0.105);Gain of phosphorylation at Y49 (P = 0.105);Gain of phosphorylation at Y49 (P = 0.105);Gain of phosphorylation at Y49 (P = 0.105);Gain of phosphorylation at Y49 (P = 0.105);

MVP

0.061

MPC

0.037

ClinPred

0.088

GERP RS

-0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over