11-18034678-T-C

Variant names:

• chr11-18034678-T-C
• rs172423
• NM_004179.3:c.301+1281A>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+1281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,086 control chromosomes in the GnomAD database, including 3,386 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 0.19 (3386 hom., cov: 32)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.301+1281A>G		intron_variant	Intron 3 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.301+1281A>G		intron_variant	Intron 3 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29209 AN: 151968 Hom.: 3384 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.192 AC: 29212 AN: 152086 Hom.: 3386 Cov.: 32 AF XY: 0.194 AC XY: 14413 AN XY: 74340

African (AFR) AF: 0.0670 AC: 2783 AN: 41514

American (AMR) AF: 0.167 AC: 2548 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1007 AN: 5172

South Asian (SAS) AF: 0.180 AC: 868 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3135 AN: 10556

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17374 AN: 67972

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.234 Hom.: 5726

Bravo AF: 0.180

Asia WGS AF: 0.184 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.18
DANN	Benign	0.81
PhyloP100		-0.83
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: rs172423; hg19: chr11-18056225;