1-181050019-A-C

Variant names:

• chr1-181050019-A-C
• rs201398297
• NM_001385161.1:c.337A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001385161.1(MR1):​c.337A>C​(p.Thr113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T113A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MR1 NM_001385161.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MR1	NM_001385161.1	c.337A>C	p.Thr113Pro	missense_variant	Exon 3 of 6	ENST00000367580.6	NP_001372090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MR1	ENST00000367580.6	c.337A>C	p.Thr113Pro	missense_variant	Exon 3 of 6	1	NM_001385161.1	ENSP00000356552.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.337A>C (p.T113P) alteration is located in exon 4 (coding exon 3) of the MR1 gene. This alteration results from a A to C substitution at nucleotide position 337, causing the threonine (T) at amino acid position 113 to be replaced by a proline (P). 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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;.;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.79	T;T;T;.;.
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.92	D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.7	H;H;H;H;H
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.9	.;.;D;D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	.;.;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;D
Polyphen		1.0	D;D;.;D;D
Vest4		0.66
MutPred		0.73		Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.39
MPC		0.28
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.97
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201398297; hg19: chr1-181019155;