Variant rs8192553 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005959.5(MTNR1B):c.692G>A(p.Arg231His) variant causes a missense change. The variant allele was found at a frequency of 0.00613 in 1,614,166 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 33 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

MTNR1B (HGNC:7464): (melatonin receptor 1B) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin. [provided by RefSeq, Jul 2008]

MTNR1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010777742).

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTNR1B	NM_005959.5 linkuse as main transcript	c.692G>A	p.Arg231His	missense_variant	2/2	ENST00000257068.3
MTNR1B	XM_011542839.3 linkuse as main transcript	c.692G>A	p.Arg231His	missense_variant	2/3
MTNR1B	XM_017017777.2 linkuse as main transcript	c.566G>A	p.Arg189His	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTNR1B	ENST00000257068.3 linkuse as main transcript	c.692G>A	p.Arg231His	missense_variant	2/2	1	NM_005959.5	P1
MTNR1B	ENST00000528076.1 linkuse as main transcript	c.166-2892G>A		intron_variant		3
MTNR1B	ENST00000532482.1 linkuse as main transcript	c.*583G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

594

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00393

AC:

988

AN:

251336

Hom.:

AF XY:

0.00406

AC XY:

552

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00565

Gnomad NFE exome

AF:

0.00662

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00636

AC:

9293

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00617

AC XY:

4488

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000788

Gnomad4 FIN exome

AF:

0.00465

Gnomad4 NFE exome

AF:

0.00770

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152326

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.00669

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.00385

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00663

AC:

ExAC

AF:

0.00385

AC:

467

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

-0.066

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0068

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.12

Sift

Uncertain

0.015

Sift4G

Uncertain

0.0020

Polyphen

0.27

Vest4

0.14

MVP

0.63

MPC

0.24

ClinPred

0.053

GERP RS

0.29

Varity_R

0.18

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over