rs11179023

Variant names:

• chr12-71978617-G-A
• rs11179023
• NM_173353.4:c.806-335G>A

Variant summary

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

The NM_173353.4(TPH2):​c.806-335G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,092 control chromosomes in the GnomAD database, including 5,636 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 0.26 (5636 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

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.806-335G>A		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.806-335G>A		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40114 AN: 151974 Hom.: 5628 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.264 AC: 40157 AN: 152092 Hom.: 5636 Cov.: 32 AF XY: 0.268 AC XY: 19960 AN XY: 74342

African (AFR) AF: 0.199 AC: 8247 AN: 41504

American (AMR) AF: 0.327 AC: 4998 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2433 AN: 5166

South Asian (SAS) AF: 0.372 AC: 1787 AN: 4810

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10560

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.268 AC: 18224 AN: 67976

Other (OTH) AF: 0.267 AC: 564 AN: 2114

Alfa AF: 0.271 Hom.: 2974

Bravo AF: 0.265

Asia WGS AF: 0.413 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.026
DANN	Benign	0.53
PhyloP100		-2.4
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: rs11179023; hg19: chr12-72372397;