rs17110489

Variant names:

• chr12-71954226-T-C
• rs17110489
• NM_173353.4:c.608+4571T>C

Variant summary

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

The NM_173353.4(TPH2):​c.608+4571T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,998 control chromosomes in the GnomAD database, including 4,113 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 0.23 (4113 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.421
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.608+4571T>C		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.750+4571T>C		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.608+4571T>C		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.618+4571T>C		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34429 AN: 151880 Hom.: 4115 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.227 AC: 34433 AN: 151998 Hom.: 4113 Cov.: 32 AF XY: 0.226 AC XY: 16818 AN XY: 74292

African (AFR) AF: 0.156 AC: 6458 AN: 41454

American (AMR) AF: 0.232 AC: 3553 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 844 AN: 3466

East Asian (EAS) AF: 0.336 AC: 1730 AN: 5146

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4810

European-Finnish (FIN) AF: 0.240 AC: 2533 AN: 10558

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17408 AN: 67968

Other (OTH) AF: 0.222 AC: 469 AN: 2108

Alfa AF: 0.241 Hom.: 5808

Bravo AF: 0.224

Asia WGS AF: 0.230 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		-0.42
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: rs17110489; hg19: chr12-72348006;