rs9325202

Variant names:

• chr12-72013697-A-G
• rs9325202
• NM_173353.4:c.1069-8702A>G

Variant summary

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

The NM_173353.4(TPH2):​c.1069-8702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,022 control chromosomes in the GnomAD database, including 23,771 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 0.55 (23771 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-8702A>G		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-8702A>G		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84268 AN: 151904 Hom.: 23750 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.555 AC: 84333 AN: 152022 Hom.: 23771 Cov.: 32 AF XY: 0.557 AC XY: 41385 AN XY: 74302

African (AFR) AF: 0.450 AC: 18652 AN: 41448

American (AMR) AF: 0.625 AC: 9551 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2235 AN: 3468

East Asian (EAS) AF: 0.614 AC: 3170 AN: 5166

South Asian (SAS) AF: 0.661 AC: 3187 AN: 4820

European-Finnish (FIN) AF: 0.521 AC: 5498 AN: 10558

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39990 AN: 67972

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.587 Hom.: 119322

Bravo AF: 0.556

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.026
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: rs9325202; hg19: chr12-72407477;