rs10784941

Variant names:

• chr12-71942732-A-G
• rs10784941
• NM_173353.4:c.255+999A>G

Variant summary

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

The NM_173353.4(TPH2):​c.255+999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,118 control chromosomes in the GnomAD database, including 13,731 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 0.40 (13731 hom., cov: 33)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.255+999A>G		intron_variant	Intron 2 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.397+999A>G		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.255+999A>G		intron_variant	Intron 2 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.265+999A>G		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60677 AN: 152000 Hom.: 13728 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.399 AC: 60693 AN: 152118 Hom.: 13731 Cov.: 33 AF XY: 0.404 AC XY: 30013 AN XY: 74380

African (AFR) AF: 0.175 AC: 7262 AN: 41516

American (AMR) AF: 0.480 AC: 7336 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1695 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2176 AN: 5174

South Asian (SAS) AF: 0.389 AC: 1875 AN: 4816

European-Finnish (FIN) AF: 0.537 AC: 5679 AN: 10568

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33142 AN: 67982

Other (OTH) AF: 0.439 AC: 929 AN: 2114

Alfa AF: 0.425 Hom.: 5228

Bravo AF: 0.387

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.38
PhyloP100		-0.36
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: rs10784941; hg19: chr12-72336512;