11-92981951-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005959.5(MTNR1B):c.728A>G(p.Lys243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,614,164 control chromosomes in the GnomAD database, including 2,997 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.087 ( 1227 hom., cov: 33)
Exomes 𝑓: 0.033 ( 1770 hom. )
Consequence
MTNR1B
NM_005959.5 missense
NM_005959.5 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.170
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.00430429).
BP6
?
Variant 11-92981951-A-G is Benign according to our data. Variant chr11-92981951-A-G is described in ClinVar as [Benign]. Clinvar id is 3060517.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTNR1B | NM_005959.5 | c.728A>G | p.Lys243Arg | missense_variant | 2/2 | ENST00000257068.3 | |
MTNR1B | XM_011542839.3 | c.728A>G | p.Lys243Arg | missense_variant | 2/3 | ||
MTNR1B | XM_017017777.2 | c.602A>G | p.Lys201Arg | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTNR1B | ENST00000257068.3 | c.728A>G | p.Lys243Arg | missense_variant | 2/2 | 1 | NM_005959.5 | P1 | |
MTNR1B | ENST00000528076.1 | c.166-2856A>G | intron_variant | 3 | |||||
MTNR1B | ENST00000532482.1 | c.*619A>G | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0865 AC: 13168AN: 152160Hom.: 1225 Cov.: 33
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GnomAD3 exomes AF: 0.0395 AC: 9930AN: 251458Hom.: 572 AF XY: 0.0351 AC XY: 4769AN XY: 135908
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GnomAD4 exome AF: 0.0326 AC: 47627AN: 1461886Hom.: 1770 Cov.: 31 AF XY: 0.0314 AC XY: 22853AN XY: 727244
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GnomAD4 genome ? AF: 0.0866 AC: 13185AN: 152278Hom.: 1227 Cov.: 33 AF XY: 0.0836 AC XY: 6226AN XY: 74472
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111
ESP6500AA
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1033
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5116
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MTNR1B-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 06, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at