rs1487280

Variant names:

• chr12-72025047-C-T
• rs1487280
• NM_173353.4:c.1164+2553C>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.1164+2553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,804 control chromosomes in the GnomAD database, including 22,184 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 0.52 (22184 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 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.1164+2553C>T		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.1164+2553C>T		intron	N/A	ENSP00000329093.3	Q8IWU9-1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79634 AN: 151686 Hom.: 22176 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.525 AC: 79675 AN: 151804 Hom.: 22184 Cov.: 31 AF XY: 0.520 AC XY: 38591 AN XY: 74166

African (AFR) AF: 0.336 AC: 13923 AN: 41378

American (AMR) AF: 0.548 AC: 8357 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2104 AN: 3466

East Asian (EAS) AF: 0.476 AC: 2452 AN: 5148

South Asian (SAS) AF: 0.519 AC: 2490 AN: 4796

European-Finnish (FIN) AF: 0.500 AC: 5258 AN: 10510

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43127 AN: 67954

Other (OTH) AF: 0.560 AC: 1182 AN: 2110

Alfa AF: 0.568 Hom.: 3176

Bravo AF: 0.521

Asia WGS AF: 0.478 AC: 1661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.67
PhyloP100		-0.068
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1487280;

hg19: chr12-72418827;