Genetic Variant NM_001385161.1:c.340T>C (chr1-181050022-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001385161.1(MR1):c.340T>C(p.Tyr114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,612,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

MR1
NM_001385161.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.400

Publications

0 publications found

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 was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385161.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MR1	NM_001385161.1	MANE Select	c.340T>C	p.Tyr114His	missense	Exon 3 of 6	NP_001372090.1	Q95460-1
MR1	NM_001531.3		c.340T>C	p.Tyr114His	missense	Exon 4 of 7	NP_001522.1	Q95460-1
MR1	NM_001385162.1		c.340T>C	p.Tyr114His	missense	Exon 3 of 6	NP_001372091.1	A0A8C8PVM5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MR1	ENST00000367580.6	TSL:1 MANE Select	c.340T>C	p.Tyr114His	missense	Exon 3 of 6	ENSP00000356552.5	Q95460-1
MR1	ENST00000282990.10	TSL:1	c.340T>C	p.Tyr114His	missense	Exon 3 of 5	ENSP00000282990.6	Q95460-3
MR1	ENST00000367579.7	TSL:1	c.329-124T>C		intron	N/A	ENSP00000356551.3	Q95460-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

250616

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1460210

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726408

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4496

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

1111912

Other (OTH)

AF:

0.00

AC:

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74380

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0112904), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.395

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.079

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PhyloP100

-0.40

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.20

Sift

Uncertain

0.014

Sift4G

Uncertain

0.013

Polyphen

0.99

Vest4

0.59

MutPred

0.42

Gain of disorder (P = 0.0143)

MVP

0.14

MPC

0.27

ClinPred

0.81

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.69

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over