rs2281820

Variant names:

• chr6-33801120-A-G
• rs2281820
• NM_002418.3:c.44T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002418.3(MLN):​c.44T>C​(p.Val15Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,613,254 control chromosomes in the GnomAD database, including 284,058 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V15I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.57 (25115 hom., cov: 33)
  • Exomes 𝑓: 0.59 (258943 hom.)
• Consequence: MLN NM_002418.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 48 publications found

Genes affected

MLN (HGNC:7141): (motilin) This gene encodes a small peptide hormone that is secreted by cells of the small intestine to regulate gastrointestinal contractions and motility. Proteolytic processing of the secreted protein produces the mature peptide and a byproduct referred to as motilin-associated peptide (MAP). Three transcript variants encoding different preproprotein isoforms but the same mature peptide have been found for this gene. [provided by RefSeq, May 2010]

ENSG00000287089 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.519E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MLN	NM_002418.3	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5	ENST00000430124.7	NP_002409.1
MLN	NM_001040109.2	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5		NP_001035198.1
MLN	NM_001184698.2	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5		NP_001171627.1
LOC105375024	XR_926707.3	n.3779-347A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MLN	ENST00000430124.7	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5	1	NM_002418.3	ENSP00000388825.2
MLN	ENST00000507738.1	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5	1		ENSP00000425467.1
MLN	ENST00000266003.9	c.44T>C	p.Val15Ala	missense_variant	Exon 2 of 5	5		ENSP00000266003.5
ENSG00000287089	ENST00000664739.1	n.979A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86666 AN: 152062 Hom.: 25082 Cov.: 33

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.607 AC: 152579 AN: 251288 AF XY: 0.616

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.599

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.584

Gnomad OTH exome AF: 0.597

GnomAD4 exome AF: 0.592 AC: 864468 AN: 1461074 Hom.: 258943 Cov.: 45 AF XY: 0.597 AC XY: 434084 AN XY: 726922

African (AFR) AF: 0.495 AC: 16558 AN: 33458

American (AMR) AF: 0.535 AC: 23916 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 15629 AN: 26126

East Asian (EAS) AF: 0.835 AC: 33149 AN: 39688

South Asian (SAS) AF: 0.725 AC: 62568 AN: 86246

European-Finnish (FIN) AF: 0.560 AC: 29845 AN: 53316

Middle Eastern (MID) AF: 0.634 AC: 3651 AN: 5762

European-Non Finnish (NFE) AF: 0.578 AC: 642839 AN: 1111404

Other (OTH) AF: 0.601 AC: 36313 AN: 60372

GnomAD4 genome AF: 0.570 AC: 86757 AN: 152180 Hom.: 25115 Cov.: 33 AF XY: 0.570 AC XY: 42403 AN XY: 74390

African (AFR) AF: 0.502 AC: 20836 AN: 41514

American (AMR) AF: 0.548 AC: 8388 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2079 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4381 AN: 5172

South Asian (SAS) AF: 0.737 AC: 3554 AN: 4822

European-Finnish (FIN) AF: 0.560 AC: 5932 AN: 10594

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39560 AN: 67986

Other (OTH) AF: 0.614 AC: 1299 AN: 2114

Alfa AF: 0.585 Hom.: 121089

Bravo AF: 0.566

TwinsUK AF: 0.585 AC: 2171

ALSPAC AF: 0.592 AC: 2280

ESP6500AA AF: 0.506 AC: 2229

ESP6500EA AF: 0.581 AC: 4994

ExAC AF: 0.609 AC: 73965

Asia WGS AF: 0.752 AC: 2616 AN: 3478

EpiCase AF: 0.594

EpiControl AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.44
DANN	Benign	0.46
DEOGEN2	Benign	0.025	T;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.060	T;T;T
MetaRNN	Benign	8.5e-7	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N
PhyloP100		-0.58
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.049
MPC		0.27
ClinPred		0.0068	T
GERP RS		-1.1
Varity_R		0.044
gMVP		0.54
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: rs2281820; hg19: chr6-33768897; COSMIC: COSV107232523;