17-76459919-A-G

Variant names:

• chr17-76459919-A-G
• rs11077823
• ENST00000250615.7:c.-456+553A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166579.2(AANAT):​c.-456+553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,202 control chromosomes in the GnomAD database, including 55,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (55721 hom., cov: 31)
• Consequence: AANAT NM_001166579.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166579.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	NM_001166579.2		c.-456+553A>G		intron	N/A	NP_001160051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	ENST00000250615.7	TSL:1	c.-456+553A>G		intron	N/A	ENSP00000250615.2
	AANAT	ENST00000878873.1		c.-76+6988A>G		intron	N/A	ENSP00000548932.1
	AANAT	ENST00000915260.1		c.-352-2397A>G		intron	N/A	ENSP00000585319.1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129851 AN: 152084 Hom.: 55670 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.856

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.854 AC: 129955 AN: 152202 Hom.: 55721 Cov.: 31 AF XY: 0.858 AC XY: 63821 AN XY: 74406

African (AFR) AF: 0.788 AC: 32702 AN: 41506

American (AMR) AF: 0.885 AC: 13531 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2985 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5160 AN: 5164

South Asian (SAS) AF: 0.923 AC: 4460 AN: 4832

European-Finnish (FIN) AF: 0.900 AC: 9543 AN: 10608

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58798 AN: 68016

Other (OTH) AF: 0.857 AC: 1811 AN: 2112

Alfa AF: 0.857 Hom.: 22675

Bravo AF: 0.848

Asia WGS AF: 0.955 AC: 3319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.79
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11077823; hg19: chr17-74456001;