11-18040935-T-A

Position:

• chr11-18040935-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000250018.6(TPH1):​c.-173A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 687,316 control chromosomes in the GnomAD database, including 19,403 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 (3349 hom., cov: 32)
  • Exomes 𝑓: 0.24 (16054 hom.)
• Consequence: TPH1 ENST00000250018.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH1	NM_004179.3	c.-26-147A>T		intron_variant		ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000250018.6	c.-173A>T		5_prime_UTR_variant	1/10	1		ENSP00000250018.2
TPH1	ENST00000682019.1	c.-26-147A>T		intron_variant			NM_004179.3	ENSP00000508368.1
TPH1	ENST00000528338.1	c.5-147A>T		intron_variant		3		ENSP00000436081.2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29126 AN: 152018 Hom.: 3347 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.237 AC: 126863 AN: 535180 Hom.: 16054 Cov.: 7 AF XY: 0.235 AC XY: 66434 AN XY: 282218

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.296

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.191 AC: 29128 AN: 152136 Hom.: 3349 Cov.: 32 AF XY: 0.193 AC XY: 14337 AN XY: 74366

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.205

Alfa AF: 0.220 Hom.: 514

Bravo AF: 0.180

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488682; hg19: chr11-18062482;