Variant rs1286672780 details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.55

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]

AANAT links:

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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 link	c.466G>A	p.Ala156Thr	missense_variant	Exon 4 of 4	ENST00000392492.8	NP_001079.1	Q16613-1F1T0I5
AANAT	NM_001166579.2 link	c.601G>A	p.Ala201Thr	missense_variant	Exon 7 of 7		NP_001160051.1	Q16613-2
AANAT	NR_110548.2 link	n.722G>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AANAT	ENST00000392492.8 link	c.466G>A	p.Ala156Thr	missense_variant	Exon 4 of 4	1	NM_001088.3	ENSP00000376282.2	Q16613-1
AANAT	ENST00000250615.7 link	c.601G>A	p.Ala201Thr	missense_variant	Exon 7 of 7	1		ENSP00000250615.2	Q16613-2
AANAT	ENST00000587798.1 link	n.*243G>A		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000468239.1	K7ERF6
AANAT	ENST00000587798.1 link	n.*243G>A		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000468239.1	K7ERF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451584

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721352

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

.;M

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.28

Sift

Benign

0.075

T;T

Sift4G

Uncertain

0.021

D;D

Polyphen

0.99

.;D

Vest4

0.41

MutPred

0.63

.;Gain of phosphorylation at A156 (P = 0.1062);

MVP

0.35

MPC

0.32

ClinPred

0.96

GERP RS

5.1

Varity_R

0.75

gMVP

0.77

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over