dbSNP rs1565177580: MTNR1B:p.Arg29Gln (chr11-92969811-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005959.5(MTNR1B):c.86G>A(p.Arg29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,416,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.837

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048462957).

BP6

Variant 11-92969811-G-A is Benign according to our data. Variant chr11-92969811-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3216985.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005959.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	NM_005959.5	MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 1 of 2	NP_005950.1	P49286

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.86G>A	p.Arg29Gln	missense	Exon 1 of 2	ENSP00000257068.2	P49286
MTNR1B	ENST00000528076.1	TSL:3	c.27G>A	p.Ala9Ala	synonymous	Exon 1 of 2	ENSP00000433573.1	H0YDG4
MTNR1B	ENST00000532482.1	TSL:5	n.86G>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000436101.1	E9PR36

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000246

AC:

AN:

203530

AF XY:

0.0000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000677

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000176

AC:

AN:

1416846

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

702098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30858

American (AMR)

AF:

0.0000971

AC:

AN:

41208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24970

East Asian (EAS)

AF:

0.00

AC:

AN:

36754

South Asian (SAS)

AF:

0.00

AC:

AN:

81386

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49200

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5478

European-Non Finnish (NFE)

AF:

0.0000184

AC:

AN:

1088828

Other (OTH)

AF:

0.00

AC:

AN:

58164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.60

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.038

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.45

M_CAP

Benign

0.011

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.49

PhyloP100

-0.84

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.11

REVEL

Benign

0.041

Sift

Benign

0.59

Sift4G

Benign

0.63

Polyphen

0.0030

Vest4

0.11

MutPred

0.35

Loss of MoRF binding (P = 0.0289)

MVP

0.35

MPC

0.18

ClinPred

0.031

GERP RS

-8.4

PromoterAI

-0.0028

Neutral

(source)

Varity_R

0.022

gMVP

0.31

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over