Variant 13-49221004-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001507.1(MLNR):c.667G>C(p.Glu223Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,378,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

MLNR
NM_001507.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.460

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082734495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MLNR	NM_001507.1 link	c.667G>C	p.Glu223Gln	missense_variant	1/2	ENST00000218721.1	NP_001498.1	O43193-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MLNR	ENST00000218721.1 link	c.667G>C	p.Glu223Gln	missense_variant	1/2	1	NM_001507.1	ENSP00000218721.1		O43193-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

154448

Hom.:

AF XY:

0.0000113

AC XY:

AN XY:

88372

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1378402

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

684504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000646

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000173

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2022

The c.667G>C (p.E223Q) alteration is located in exon 1 (coding exon 1) of the MLNR gene. This alteration results from a G to C substitution at nucleotide position 667, causing the glutamic acid (E) at amino acid position 223 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.3

DANN

Benign

0.85

DEOGEN2

Benign

0.015

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.46

M_CAP

Benign

0.059

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.42

REVEL

Benign

0.072

Sift

Benign

0.17

Sift4G

Benign

0.34

Polyphen

0.16

Vest4

0.10

MutPred

0.31

Loss of glycosylation at P222 (P = 0.0947);

MVP

0.59

ClinPred

0.052

GERP RS

0.13

Varity_R

0.053

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over