Genetic Variant MTNR1B:p.Thr168Thr (chr11-92981727-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005959.5(MTNR1B):c.504C>T(p.Thr168Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00084 in 1,614,214 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

MTNR1B
NM_005959.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-92981727-C-T is Benign according to our data. Variant chr11-92981727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719914.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.02 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1B	NM_005959.5 link	c.504C>T	p.Thr168Thr	synonymous_variant	Exon 2 of 2	ENST00000257068.3	NP_005950.1	P49286
MTNR1B	XM_011542839.3 link	c.504C>T	p.Thr168Thr	synonymous_variant	Exon 2 of 3		XP_011541141.1	P49286
MTNR1B	XM_017017777.2 link	c.378C>T	p.Thr126Thr	synonymous_variant	Exon 2 of 3		XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTNR1B	ENST00000257068.3 link	c.504C>T	p.Thr168Thr	synonymous_variant	Exon 2 of 2	1	NM_005959.5	ENSP00000257068.2	P49286
MTNR1B	ENST00000528076.1 link	c.165-3080C>T		intron_variant	Intron 1 of 1	3		ENSP00000433573.1	H0YDG4
MTNR1B	ENST00000532482.1 link	n.*395C>T		non_coding_transcript_exon_variant	Exon 3 of 3	5		ENSP00000436101.1	E9PR36
MTNR1B	ENST00000532482.1 link	n.*395C>T		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000436101.1	E9PR36

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000907

AC:

228

AN:

251398

Hom.:

AF XY:

0.000824

AC XY:

112

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00176

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000859

AC:

1256

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

587

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.000656

AC:

100

AN:

152324

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000701

Hom.:

Bravo

AF:

0.000461

EpiCase

AF:

0.000981

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MTNR1B-related disorder

Benign:1

Mar 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.4

DANN

Benign

0.51

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