rs4238989

Positions:

• chr17-76467306-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166579.2(AANAT):​c.60+1074C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,044 control chromosomes in the GnomAD database, including 17,012 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 0.45 (17012 hom., cov: 32)
• Consequence: AANAT NM_001166579.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AANAT	NM_001166579.2	c.60+1074C>G		intron_variant			NP_001160051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000250615.7	c.60+1074C>G		intron_variant		1		ENSP00000250615.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68997 AN: 151926 Hom.: 17011 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 69008 AN: 152044 Hom.: 17012 Cov.: 32 AF XY: 0.458 AC XY: 34005 AN XY: 74322

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.466

Alfa AF: 0.497 Hom.: 2447

Bravo AF: 0.437

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4238989; hg19: chr17-74463388;