rs9325202

Positions:

• chr12-72013697-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TPH2	NM_173353.4	c.1069-8702A>G		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-8702A>G		intron_variant		1	NM_173353.4	P1

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

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.584

Alfa AF: 0.595 Hom.: 60857

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9325202; hg19: chr12-72407477;