rs11615016

chr12-72022214-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.1069-185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 152,268 control chromosomes in the GnomAD database, including 317 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 0.052 (317 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.1069-185A>G		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-185A>G		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7939 AN: 152150 Hom.: 316 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0522 AC: 7941 AN: 152268 Hom.: 317 Cov.: 32 AF XY: 0.0486 AC XY: 3620 AN XY: 74458

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0762 Hom.: 300

Bravo AF: 0.0543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.039
Dann	Benign	0.46

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: rs11615016; hg19: chr12-72415994;