17-76459497-T-C

Variant summary

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

The ENST00000250615.7(AANAT):c.-456+131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,244 control chromosomes in the GnomAD database, including 51,359 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 0.81 (51343 hom., cov: 33)
  • Exomes 𝑓: 0.86 (16 hom.)
• Consequence: AANAT ENST00000250615.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AANAT	NM_001166579.2	c.-456+131T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AANAT	ENST00000250615.7	c.-456+131T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123765 AN: 152082 Hom.: 51314 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.822

GnomAD4 exome AF: 0.864 AC: 38 AN: 44 Hom.: 16 AF XY: 0.875 AC XY: 28 AN XY: 32

Gnomad4 AFR exome AF: 0.750

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.906

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.814 AC: 123837 AN: 152200 Hom.: 51343 Cov.: 33 AF XY: 0.819 AC XY: 60978 AN XY: 74432

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.861

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.824

Alfa AF: 0.846 Hom.: 22044

Bravo AF: 0.802

Asia WGS AF: 0.945 AC: 3284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.8
Dann	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11077821; hg19: chr17-74455579;