rs10748185

Variant names:

• chr12-71942075-G-A
• rs10748185
• NM_173353.4:c.255+342G>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.255+342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,960 control chromosomes in the GnomAD database, including 14,220 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 0.42 (14220 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 15 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.255+342G>A		intron_variant	Intron 2 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.397+342G>A		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.255+342G>A		intron_variant	Intron 2 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.265+342G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63796 AN: 151842 Hom.: 14212 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.420 AC: 63825 AN: 151960 Hom.: 14220 Cov.: 31 AF XY: 0.424 AC XY: 31498 AN XY: 74260

African (AFR) AF: 0.262 AC: 10876 AN: 41458

American (AMR) AF: 0.485 AC: 7406 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1673 AN: 3466

East Asian (EAS) AF: 0.419 AC: 2162 AN: 5158

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5646 AN: 10550

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32655 AN: 67938

Other (OTH) AF: 0.450 AC: 946 AN: 2102

Alfa AF: 0.457 Hom.: 8216

Bravo AF: 0.412

Asia WGS AF: 0.392 AC: 1362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.15
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: rs10748185; hg19: chr12-72335855;