rs17722134

Variant names:

• chr12-72007914-A-G
• rs17722134
• NM_173353.4:c.1068+13349A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_173353.4(TPH2):​c.1068+13349A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 152,286 control chromosomes in the GnomAD database, including 33 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 0.018 (33 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 3 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=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0181 (2753/152286) while in subpopulation NFE AF = 0.0299 (2034/68014). AF 95% confidence interval is 0.0288. There are 33 homozygotes in GnomAd4. There are 1233 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2753 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.1068+13349A>G		intron	N/A	NP_775489.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.1068+13349A>G		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2753 AN: 152168 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0299

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0181 AC: 2753 AN: 152286 Hom.: 33 Cov.: 32 AF XY: 0.0166 AC XY: 1233 AN XY: 74476

African (AFR) AF: 0.00510 AC: 212 AN: 41566

American (AMR) AF: 0.0187 AC: 286 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00747 AC: 36 AN: 4822

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2034 AN: 68014

Other (OTH) AF: 0.0189 AC: 40 AN: 2114

Alfa AF: 0.0253 Hom.: 99

Bravo AF: 0.0183

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.35
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism

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: rs17722134; hg19: chr12-72401694;