17-76459190-G-A

Position:

• chr17-76459190-G-A

Variant summary

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

The NM_001166579.2(AANAT):​c.-575-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,188 control chromosomes in the GnomAD database, including 48,894 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 0.79 (48892 hom., cov: 32)
  • Exomes 𝑓: 0.83 (2 hom.)
• Consequence: AANAT NM_001166579.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336

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=-0.82).
• 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	Protein	UniProt
AANAT	NM_001166579.2	c.-575-57G>A		intron_variant			NP_001160051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000250615.7	c.-575-57G>A		intron_variant		1		ENSP00000250615.2

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120737 AN: 152064 Hom.: 48868 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.833 AC: 5 AN: 6 Hom.: 2 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.750

GnomAD4 genome AF: 0.794 AC: 120803 AN: 152182 Hom.: 48892 Cov.: 32 AF XY: 0.800 AC XY: 59555 AN XY: 74400

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.913

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.799

Alfa AF: 0.813 Hom.: 9704

Bravo AF: 0.781

Asia WGS AF: 0.931 AC: 3236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16968964; hg19: chr17-74455272;