rs10488683

Variant names:

• chr11-18031998-C-T
• rs10488683
• NM_004179.3:c.402+1276G>A

Variant summary

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

The NM_004179.3(TPH1):​c.402+1276G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,818 control chromosomes in the GnomAD database, including 23,074 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 0.55 (23074 hom., cov: 31)
• Consequence: TPH1 NM_004179.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.402+1276G>A		intron_variant	Intron 4 of 10	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.402+1276G>A		intron_variant	Intron 4 of 10		NM_004179.3	ENSP00000508368.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83508 AN: 151702 Hom.: 23046 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.551 AC: 83583 AN: 151818 Hom.: 23074 Cov.: 31 AF XY: 0.547 AC XY: 40570 AN XY: 74140

African (AFR) AF: 0.505 AC: 20877 AN: 41360

American (AMR) AF: 0.570 AC: 8708 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2873 AN: 5174

South Asian (SAS) AF: 0.489 AC: 2349 AN: 4802

European-Finnish (FIN) AF: 0.545 AC: 5713 AN: 10486

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38917 AN: 67950

Other (OTH) AF: 0.560 AC: 1178 AN: 2104

Alfa AF: 0.562 Hom.: 7737

Bravo AF: 0.551

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.40
PhyloP100		0.27
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: rs10488683; hg19: chr11-18053545;