NM_001088.3:c.466G>A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001088.3(AANAT):c.466G>A(p.Ala156Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
AANAT
NM_001088.3 missense
NM_001088.3 missense
Scores
8
11
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.55
Genes affected
AANAT (HGNC:19): (aralkylamine N-acetyltransferase) The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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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;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AANAT | NM_001088.3 | c.466G>A | p.Ala156Thr | missense_variant | Exon 4 of 4 | ENST00000392492.8 | NP_001079.1 | |
AANAT | NM_001166579.2 | c.601G>A | p.Ala201Thr | missense_variant | Exon 7 of 7 | NP_001160051.1 | ||
AANAT | NR_110548.2 | n.722G>A | non_coding_transcript_exon_variant | Exon 4 of 4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AANAT | ENST00000392492.8 | c.466G>A | p.Ala156Thr | missense_variant | Exon 4 of 4 | 1 | NM_001088.3 | ENSP00000376282.2 | ||
AANAT | ENST00000250615.7 | c.601G>A | p.Ala201Thr | missense_variant | Exon 7 of 7 | 1 | ENSP00000250615.2 | |||
AANAT | ENST00000587798.1 | n.*243G>A | non_coding_transcript_exon_variant | Exon 4 of 4 | 5 | ENSP00000468239.1 | ||||
AANAT | ENST00000587798.1 | n.*243G>A | 3_prime_UTR_variant | Exon 4 of 4 | 5 | ENSP00000468239.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1451584Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721352
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1451584
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
721352
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
0.99
.;D
Vest4
MutPred
0.63
.;Gain of phosphorylation at A156 (P = 0.1062);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at