rs751459937

Variant names:

• chr1-181049088-C-T
• rs751459937
• NM_001385161.1:c.104C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3 BS2_Supporting

The NM_001310213.2(MR1):​c.-110C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000356 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: MR1 NM_001310213.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816
• BS2: High AC in GnomAdExome4 at 52 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001310213.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MR1	NM_001385161.1	MANE Select	c.104C>T	p.Ser35Leu	missense	Exon 2 of 6	NP_001372090.1	Q95460-1
	MR1	NM_001310213.2		c.-110C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 7	NP_001297142.1
	MR1	NM_001531.3		c.104C>T	p.Ser35Leu	missense	Exon 3 of 7	NP_001522.1	Q95460-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MR1	ENST00000367580.6	TSL:1 MANE Select	c.104C>T	p.Ser35Leu	missense	Exon 2 of 6	ENSP00000356552.5	Q95460-1
	MR1	ENST00000367579.7	TSL:1	c.104C>T	p.Ser35Leu	missense	Exon 2 of 6	ENSP00000356551.3	Q95460-2
	MR1	ENST00000282990.10	TSL:1	c.104C>T	p.Ser35Leu	missense	Exon 2 of 5	ENSP00000282990.6	Q95460-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251094 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461668 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111854

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		2.2
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.14
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.86		Gain of sheet (P = 0.1208)
MVP		0.41
MPC		0.25
ClinPred		0.70	D
GERP RS		2.9
Varity_R		0.57
gMVP		0.86
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs751459937; hg19: chr1-181018224;