Variant 11-92981635-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005959.5(MTNR1B):c.412C>T(p.Arg138Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,614,202 control chromosomes in the GnomAD database, including 4 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 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.445

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16388956).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTNR1B	NM_005959.5 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	ENST00000257068.3
MTNR1B	XM_011542839.3 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/3
MTNR1B	XM_017017777.2 linkuse as main transcript	c.286C>T	p.Arg96Cys	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTNR1B	ENST00000257068.3 linkuse as main transcript	c.412C>T	p.Arg138Cys	missense_variant	2/2	1	NM_005959.5	P1
MTNR1B	ENST00000528076.1 linkuse as main transcript	c.166-3172C>T		intron_variant		3
MTNR1B	ENST00000532482.1 linkuse as main transcript	c.*303C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00106

AC:

267

AN:

251462

Hom.:

AF XY:

0.00122

AC XY:

166

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00135

AC:

1973

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1046

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152310

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.000861

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00109

AC:

132

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.069

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.16

MetaSVM

Pathogenic

0.98

MutationAssessor

Pathogenic

4.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.5

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.60

MVP

0.95

MPC

0.56

ClinPred

0.14

GERP RS

2.1

Varity_R

0.69

gMVP

0.80

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