rs10879346

Variant names:

• chr12-71958055-C-T
• rs10879346
• NM_173353.4:c.608+8400C>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.608+8400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,092 control chromosomes in the GnomAD database, including 19,850 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 0.50 (19850 hom., cov: 34)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 8 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 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.608+8400C>T		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.608+8400C>T		intron	N/A	ENSP00000329093.3
	TPH2	ENST00000546576.1	TSL:5	n.619-3498C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76287 AN: 151974 Hom.: 19838 Cov.: 34

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.502 AC: 76325 AN: 152092 Hom.: 19850 Cov.: 34 AF XY: 0.503 AC XY: 37422 AN XY: 74366

African (AFR) AF: 0.365 AC: 15149 AN: 41452

American (AMR) AF: 0.523 AC: 7990 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3468

East Asian (EAS) AF: 0.481 AC: 2492 AN: 5184

South Asian (SAS) AF: 0.523 AC: 2522 AN: 4818

European-Finnish (FIN) AF: 0.560 AC: 5924 AN: 10580

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38313 AN: 67982

Other (OTH) AF: 0.530 AC: 1120 AN: 2114

Alfa AF: 0.538 Hom.: 45539

Bravo AF: 0.494

Asia WGS AF: 0.489 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.66
DANN	Benign	0.83
PhyloP100		-1.4
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: rs10879346; hg19: chr12-72351835; COSMIC: COSV61594774;