chr17-76469730-C-T

Variant names:

• chr17-76469730-C-T
• rs200468284
• NM_001088.3:c.384C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001088.3(AANAT):​c.384C>T​(p.Arg128Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,555,210 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00052 (9 hom.)
• Consequence: AANAT NM_001088.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0910
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 17-76469730-C-T is Benign according to our data. Variant chr17-76469730-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2648316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.091 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001088.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	NM_001088.3	MANE Select	c.384C>T	p.Arg128Arg	synonymous	Exon 4 of 4	NP_001079.1	F1T0I5
	AANAT	NM_001166579.2		c.519C>T	p.Arg173Arg	synonymous	Exon 7 of 7	NP_001160051.1	Q16613-2
	AANAT	NR_110548.2		n.640C>T		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	ENST00000392492.8	TSL:1 MANE Select	c.384C>T	p.Arg128Arg	synonymous	Exon 4 of 4	ENSP00000376282.2	Q16613-1
	AANAT	ENST00000250615.7	TSL:1	c.519C>T	p.Arg173Arg	synonymous	Exon 7 of 7	ENSP00000250615.2	Q16613-2
	AANAT	ENST00000878873.1		c.384C>T	p.Arg128Arg	synonymous	Exon 4 of 4	ENSP00000548932.1

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152232 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00105 AC: 189 AN: 179864 AF XY: 0.00137

Gnomad AFR exome AF: 0.0000882

Gnomad AMR exome AF: 0.000111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000135

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.000436

GnomAD4 exome AF: 0.000517 AC: 725 AN: 1402860 Hom.: 9 Cov.: 31 AF XY: 0.000741 AC XY: 512 AN XY: 691348

African (AFR) AF: 0.0000620 AC: 2 AN: 32266

American (AMR) AF: 0.000157 AC: 6 AN: 38132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23520

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 37972

South Asian (SAS) AF: 0.00655 AC: 514 AN: 78476

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 47976

Middle Eastern (MID) AF: 0.000972 AC: 5 AN: 5144

European-Non Finnish (NFE) AF: 0.000146 AC: 158 AN: 1081614

Other (OTH) AF: 0.000658 AC: 38 AN: 57760

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152350 Hom.: 1 Cov.: 33 AF XY: 0.000497 AC XY: 37 AN XY: 74498

African (AFR) AF: 0.0000722 AC: 3 AN: 41578

American (AMR) AF: 0.000327 AC: 5 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00641 AC: 31 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000154 Hom.: 0

Bravo AF: 0.000147

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.4
DANN	Benign	0.84
PhyloP100		0.091
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200468284; hg19: chr17-74465812; COSMIC: COSV51686118; COSMIC: COSV51686118;