rs11179003

Positions:

• chr12-71949507-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.541-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0369 in 1,154,528 control chromosomes in the GnomAD database, including 1,449 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 0.043 (206 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1243 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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]

TPH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.541-81C>T		intron_variant		ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.683-81C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.541-81C>T		intron_variant		1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.551-81C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6566 AN: 152144 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0360 AC: 36041 AN: 1002266 Hom.: 1243 AF XY: 0.0387 AC XY: 20070 AN XY: 518914

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.0534

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.0913

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.0118

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0432 AC: 6577 AN: 152262 Hom.: 206 Cov.: 32 AF XY: 0.0445 AC XY: 3311 AN XY: 74450

Gnomad4 AFR AF: 0.0638

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0310 Hom.: 102

Bravo AF: 0.0450

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.4
DANN	Benign	0.59

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: rs11179003; hg19: chr12-72343287;