rs17721739

Variant names:

• chr11-18034813-T-C
• rs17721739
• NM_004179.3:c.301+1146A>G

Variant summary

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

The NM_004179.3(TPH1):​c.301+1146A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,214 control chromosomes in the GnomAD database, including 1,607 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 0.13 (1607 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 5 publications found

Genes affected

TPH1 (HGNC:12008): (tryptophan hydroxylase 1) This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

ENSG00000302464 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.301+1146A>G		intron	N/A	NP_004170.1	P17752-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	ENST00000682019.1	MANE Select	c.301+1146A>G		intron	N/A	ENSP00000508368.1	P17752-1
	TPH1	ENST00000250018.6	TSL:1	c.301+1146A>G		intron	N/A	ENSP00000250018.2	P17752-1
	TPH1	ENST00000417164.5	TSL:1	n.301+1146A>G		intron	N/A	ENSP00000403831.1	E7EMX4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20063 AN: 152096 Hom.: 1610 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0976

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.132 AC: 20060 AN: 152214 Hom.: 1607 Cov.: 32 AF XY: 0.127 AC XY: 9420 AN XY: 74416

African (AFR) AF: 0.0486 AC: 2020 AN: 41560

American (AMR) AF: 0.159 AC: 2427 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3472

East Asian (EAS) AF: 0.0978 AC: 507 AN: 5184

South Asian (SAS) AF: 0.155 AC: 744 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1095 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12272 AN: 67984

Other (OTH) AF: 0.148 AC: 312 AN: 2108

Alfa AF: 0.146 Hom.: 213

Bravo AF: 0.131

Asia WGS AF: 0.139 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		1.0
Mutation Taster		=30/70	disease causing

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: rs17721739; hg19: chr11-18056360;