17-76467027-G-T

Variant names:

• chr17-76467027-G-T
• rs3760138
• ENST00000250615.7:c.60+795G>T

Variant summary

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

The ENST00000250615.7(AANAT):​c.60+795G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,660 control chromosomes in the GnomAD database, including 15,713 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 0.44 (15713 hom., cov: 30)
• Consequence: AANAT ENST00000250615.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.895
• Publications: 18 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AANAT	NM_001166579.2	c.60+795G>T		intron_variant	Intron 4 of 6		NP_001160051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000250615.7	c.60+795G>T		intron_variant	Intron 4 of 6	1		ENSP00000250615.2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67199 AN: 151542 Hom.: 15712 Cov.: 30

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.443 AC: 67216 AN: 151660 Hom.: 15713 Cov.: 30 AF XY: 0.445 AC XY: 32957 AN XY: 74124

African (AFR) AF: 0.274 AC: 11318 AN: 41340

American (AMR) AF: 0.514 AC: 7832 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1531 AN: 5144

South Asian (SAS) AF: 0.440 AC: 2117 AN: 4810

European-Finnish (FIN) AF: 0.554 AC: 5818 AN: 10496

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35533 AN: 67866

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.475 Hom.: 7305

Bravo AF: 0.431

Asia WGS AF: 0.413 AC: 1435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.89
PhyloP100		0.90
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: rs3760138; hg19: chr17-74463109;