rs11179000

Variant names:

• chr12-71944848-A-T
• rs11179000
• NM_173353.4:c.540+162A>T

Variant summary

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

The NM_173353.4(TPH2):​c.540+162A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,088 control chromosomes in the GnomAD database, including 8,213 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 0.31 (8213 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• Publications: 19 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).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.540+162A>T		intron_variant	Intron 4 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.682+162A>T		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.540+162A>T		intron_variant	Intron 4 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.550+162A>T		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47379 AN: 151970 Hom.: 8195 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.312 AC: 47430 AN: 152088 Hom.: 8213 Cov.: 32 AF XY: 0.312 AC XY: 23168 AN XY: 74350

African (AFR) AF: 0.435 AC: 18011 AN: 41450

American (AMR) AF: 0.329 AC: 5027 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3472

East Asian (EAS) AF: 0.533 AC: 2761 AN: 5178

South Asian (SAS) AF: 0.332 AC: 1604 AN: 4828

European-Finnish (FIN) AF: 0.203 AC: 2147 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16016 AN: 67986

Other (OTH) AF: 0.298 AC: 631 AN: 2114

Alfa AF: 0.283 Hom.: 800

Bravo AF: 0.325

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.23
PhyloP100		-0.69
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: rs11179000; hg19: chr12-72338628;