13-49220514-C-A

Variant names:

• chr13-49220514-C-A
• rs9568169
• NM_001507.1:c.177C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• Publications: 15 publications found

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]

ENSG00000288743 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001507.1. 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
	MLNR	NM_001507.1	MANE Select	c.177C>A	p.Thr59Thr	synonymous	Exon 1 of 2	NP_001498.1	O43193-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MLNR	ENST00000218721.1	TSL:1 MANE Select	c.177C>A	p.Thr59Thr	synonymous	Exon 1 of 2	ENSP00000218721.1	O43193-1
	MLNR	ENST00000850988.1		c.177C>A	p.Thr59Thr	synonymous	Exon 1 of 2	ENSP00000521070.1
	ENSG00000288743	ENST00000719188.1		n.375+14373G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47852 AN: 151844 Hom.: 7704 Cov.: 32

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

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.: 38 AF XY: 0.327 AC XY: 235923 AN XY: 721426

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

GnomAD4 genome AF: 0.315 AC: 47858 AN: 151962 Hom.: 7710 Cov.: 32 AF XY: 0.318 AC XY: 23609 AN XY: 74266

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	1.4
DANN	Benign	0.88
PhyloP100		-0.93
PromoterAI		-0.055	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs9568169; hg19: chr13-49794650; COSMIC: COSV54532305;