NM_001088.3:c.366T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate

The NM_001088.3(AANAT):ā€‹c.366T>Gā€‹(p.His122Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AANAT
NM_001088.3 missense

Scores

5
8
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320
Variant links:
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 Likely_pathogenic. Variant got 6 ACMG points.

PM1
In a site Important for the catalytic mechanism; involved in substrate deprotonation (size 0) in uniprot entity SNAT_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AANATNM_001088.3 linkc.366T>G p.His122Gln missense_variant Exon 4 of 4 ENST00000392492.8 NP_001079.1 Q16613-1F1T0I5
AANATNM_001166579.2 linkc.501T>G p.His167Gln missense_variant Exon 7 of 7 NP_001160051.1 Q16613-2
AANATNR_110548.2 linkn.622T>G non_coding_transcript_exon_variant Exon 4 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AANATENST00000392492.8 linkc.366T>G p.His122Gln missense_variant Exon 4 of 4 1 NM_001088.3 ENSP00000376282.2 Q16613-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1385700
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
680376
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.67
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.57
.;D
Eigen
Benign
-0.17
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.042
D
MetaRNN
Pathogenic
0.91
D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.8
.;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-7.2
D;D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.84
MutPred
0.70
.;Gain of MoRF binding (P = 0.0853);
MVP
0.27
MPC
0.35
ClinPred
0.99
D
GERP RS
-1.0
Varity_R
0.85
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs140194920; hg19: chr17-74465794; API