12-71941293-G-T

Variant names:

• chr12-71941293-G-T
• rs4341581
• NM_173353.4:c.106-291G>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.106-291G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 152,240 control chromosomes in the GnomAD database, including 71,896 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 0.97 (71896 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.106-291G>T		intron_variant	Intron 1 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.248-291G>T		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.106-291G>T		intron_variant	Intron 1 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.116-291G>T		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.972 AC: 147799 AN: 152122 Hom.: 71836 Cov.: 31

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.975

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

GnomAD4 genome AF: 0.972 AC: 147918 AN: 152240 Hom.: 71896 Cov.: 31 AF XY: 0.971 AC XY: 72232 AN XY: 74420

African (AFR) AF: 0.994 AC: 41286 AN: 41552

American (AMR) AF: 0.979 AC: 14961 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3333 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.993 AC: 4785 AN: 4820

European-Finnish (FIN) AF: 0.918 AC: 9727 AN: 10592

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.962 AC: 65419 AN: 68024

Other (OTH) AF: 0.975 AC: 2057 AN: 2110

Alfa AF: 0.970 Hom.: 9018

Bravo AF: 0.975

Asia WGS AF: 0.994 AC: 3457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.2
DANN	Benign	0.24
PhyloP100		1.7
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: rs4341581; hg19: chr12-72335073;