11-92969849-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005959.5(MTNR1B):ā€‹c.124G>Cā€‹(p.Ala42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,609,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

1
3
15

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 0.0250
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MTNR1BNM_005959.5 linkuse as main transcriptc.124G>C p.Ala42Pro missense_variant 1/2 ENST00000257068.3 NP_005950.1
MTNR1BXM_011542839.3 linkuse as main transcriptc.124G>C p.Ala42Pro missense_variant 1/3 XP_011541141.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTNR1BENST00000257068.3 linkuse as main transcriptc.124G>C p.Ala42Pro missense_variant 1/21 NM_005959.5 ENSP00000257068 P1
MTNR1BENST00000528076.1 linkuse as main transcriptc.68G>C p.Ser23Thr missense_variant 1/23 ENSP00000433573
MTNR1BENST00000532482.1 linkuse as main transcriptc.124G>C p.Ala42Pro missense_variant, NMD_transcript_variant 1/35 ENSP00000436101

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457802
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
724952
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: risk factor
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMJan 29, 2012- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
0.010
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
17
DANN
Benign
0.43
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.13
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.014
T
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.28
Sift
Benign
0.069
T
Sift4G
Benign
0.12
T
Polyphen
0.92
P
Vest4
0.78
MutPred
0.70
Gain of glycosylation at A42 (P = 0.0072);
MPC
0.46
ClinPred
0.87
D
GERP RS
-1.1
Varity_R
0.12
gMVP
0.78

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.

Other links and lift over

dbSNP: rs387906779; hg19: chr11-92703015; API