Genetic Variant MLNR:p.Thr59Thr (chr13-49220514-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001507.1(MLNR):c.177C>A(p.Thr59Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,603,658 control chromosomes in the GnomAD database, including 85,173 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7710 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77463 hom. )

Consequence

MLNR
NM_001507.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.932

Publications

15 publications found

Variant links:

Genes affected

MLNR (HGNC:4495): (motilin receptor) Motilin is a 22 amino acid peptide hormone expressed throughout the gastrointestinal (GI) tract. The protein encoded by this gene is a motilin receptor which is a member of the G-protein coupled receptor 1 family. This member is a multi-pass transmembrane protein, and is an important therapeutic target for the treatment of hypomotility disorders. [provided by RefSeq, Aug 2011]

MLNR links:

ENSG00000288743 (HGNC:):

ENSG00000288743 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP7

Synonymous conserved (PhyloP=-0.932 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLNR	NM_001507.1 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 1 of 2	ENST00000218721.1	NP_001498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLNR	ENST00000218721.1 link	c.177C>A	p.Thr59Thr	synonymous_variant	Exon 1 of 2	1	NM_001507.1	ENSP00000218721.1

Frequencies

GnomAD3 genomes

AF:

0.315

AC:

47852

AN:

151844

Hom.:

7704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.497

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.344

AC:

78189

AN:

227320

AF XY:

0.353

show subpopulations

Gnomad AFR exome

AF:

0.289

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.321

AC:

466694

AN:

1451696

Hom.:

77463

Cov.:

AF XY:

0.327

AC XY:

235923

AN XY:

721426

show subpopulations

African (AFR)

AF:

0.282

AC:

9333

AN:

33088

American (AMR)

AF:

0.317

AC:

13824

AN:

43612

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

8520

AN:

25976

East Asian (EAS)

AF:

0.493

AC:

19127

AN:

38782

South Asian (SAS)

AF:

0.489

AC:

41483

AN:

84752

European-Finnish (FIN)

AF:

0.297

AC:

15525

AN:

52188

Middle Eastern (MID)

AF:

0.363

AC:

2093

AN:

5758

European-Non Finnish (NFE)

AF:

0.305

AC:

337343

AN:

1107562

Other (OTH)

AF:

0.324

AC:

19446

AN:

59978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

19127

38255

57382

76510

95637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11242

22484

33726

44968

56210

<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:

0.315

AC:

47858

AN:

151962

Hom.:

7710

Cov.:

AF XY:

0.318

AC XY:

23609

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.292

AC:

12087

AN:

41446

American (AMR)

AF:

0.296

AC:

4519

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1122

AN:

3472

East Asian (EAS)

AF:

0.480

AC:

2466

AN:

5138

South Asian (SAS)

AF:

0.498

AC:

2399

AN:

4822

European-Finnish (FIN)

AF:

0.299

AC:

3167

AN:

10578

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.309

AC:

21011

AN:

67918

Other (OTH)

AF:

0.321

AC:

676

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1699

3398

5096

6795

8494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.305

Hom.:

11059

Bravo

AF:

0.310

Asia WGS

AF:

0.471

AC:

1639

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

1.4

(source)

DANN

Benign

0.88

PhyloP100

-0.93

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over