chr4-186555211-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP4
The NM_005958.4(MTNR1A):āc.155T>Cā(p.Val52Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00085 in 1,595,184 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00053 ( 0 hom., cov: 32)
Exomes š: 0.00088 ( 1 hom. )
Consequence
MTNR1A
NM_005958.4 missense
NM_005958.4 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 8.55
Genes affected
MTNR1A (HGNC:7463): (melatonin receptor 1A) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G-protein coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive effects of melatonin. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
BP4
Computational evidence support a benign effect (MetaRNN=0.31527254).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTNR1A | NM_005958.4 | c.155T>C | p.Val52Ala | missense_variant | 1/2 | ENST00000307161.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTNR1A | ENST00000307161.5 | c.155T>C | p.Val52Ala | missense_variant | 1/2 | 1 | NM_005958.4 | P1 | |
MTNR1A | ENST00000703170.1 | c.155T>C | p.Val52Ala | missense_variant | 1/2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000533 AC: 81AN: 152084Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000589 AC: 128AN: 217488Hom.: 0 AF XY: 0.000629 AC XY: 74AN XY: 117688
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GnomAD4 exome AF: 0.000884 AC: 1275AN: 1442982Hom.: 1 Cov.: 31 AF XY: 0.000884 AC XY: 633AN XY: 716172
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GnomAD4 genome AF: 0.000532 AC: 81AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74412
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2022 | The c.155T>C (p.V52A) alteration is located in exon 1 (coding exon 1) of the MTNR1A gene. This alteration results from a T to C substitution at nucleotide position 155, causing the valine (V) at amino acid position 52 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MVP
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