rs1386493

Variant names:

• chr12-71961399-A-G
• rs1386493
• NM_173353.4:c.609-11120A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-71961399-A-G
• chr12-71961399-A-T

Variant summary

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

The NM_173353.4(TPH2):​c.609-11120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,176 control chromosomes in the GnomAD database, including 47,337 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 (47337 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 26 publications found

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

TPH2 Gene-Disease associations (from GenCC):

• attention deficit-hyperactivity disorder, susceptibility to, 7

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173353.4. 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
	TPH2	NM_173353.4	MANE Select	c.609-11120A>G		intron	N/A	NP_775489.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.609-11120A>G		intron	N/A	ENSP00000329093.3	Q8IWU9-1
	TPH2	ENST00000546576.1	TSL:5	n.619-154A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119615 AN: 152058 Hom.: 47309 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.787 AC: 119687 AN: 152176 Hom.: 47337 Cov.: 32 AF XY: 0.786 AC XY: 58489 AN XY: 74400

African (AFR) AF: 0.701 AC: 29091 AN: 41504

American (AMR) AF: 0.784 AC: 11983 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2942 AN: 3472

East Asian (EAS) AF: 0.832 AC: 4303 AN: 5174

South Asian (SAS) AF: 0.780 AC: 3764 AN: 4824

European-Finnish (FIN) AF: 0.811 AC: 8587 AN: 10594

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56269 AN: 67996

Other (OTH) AF: 0.801 AC: 1692 AN: 2112

Alfa AF: 0.803 Hom.: 7618

Bravo AF: 0.782

Asia WGS AF: 0.743 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.55
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1386493; hg19: chr12-72355179;