chr1-181034047-G-A

Position:

• chr1-181034047-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001310213.2(MR1):​c.-290G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MR1 NM_001310213.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0700

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]

ACMG classification

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=0.16804406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MR1	NM_001385161.1	c.40G>A	p.Val14Met	missense_variant	1/6	ENST00000367580.6	NP_001372090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MR1	ENST00000367580.6	c.40G>A	p.Val14Met	missense_variant	1/6	1	NM_001385161.1	ENSP00000356552.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.40G>A (p.V14M) alteration is located in exon 2 (coding exon 1) of the MR1 gene. This alteration results from a G to A substitution at nucleotide position 40, causing the valine (V) at amino acid position 14 to be replaced by a methionine (M). 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	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.76	T;T;T;T;.;.
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L;L;L;L;L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.55	.;.;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.031	.;.;D;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.98	D;D;.;D;D;D
Vest4		0.30
MutPred		0.38		Loss of stability (P = 0.1049);Loss of stability (P = 0.1049);Loss of stability (P = 0.1049);Loss of stability (P = 0.1049);Loss of stability (P = 0.1049);Loss of stability (P = 0.1049);
MVP		0.11
MPC		0.12
ClinPred		0.46	T
GERP RS		1.9
Varity_R		0.047
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-181003183;