chr11-18040935-T-A

Variant names:

• chr11-18040935-T-A
• rs10488682
• ENST00000250018.6:c.-173A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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 = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000250018.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.-26-147A>T		intron	N/A	NP_004170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	ENST00000250018.6	TSL:1	c.-173A>T		5_prime_UTR	Exon 1 of 10	ENSP00000250018.2
	TPH1	ENST00000682019.1	MANE Select	c.-26-147A>T		intron	N/A	ENSP00000508368.1
	TPH1	ENST00000528338.2	TSL:3	c.5-147A>T		intron	N/A	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

African (AFR) AF: 0.0699 AC: 936 AN: 13392

American (AMR) AF: 0.167 AC: 3061 AN: 18306

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 2615 AN: 13338

East Asian (EAS) AF: 0.116 AC: 3120 AN: 26828

South Asian (SAS) AF: 0.181 AC: 8630 AN: 47690

European-Finnish (FIN) AF: 0.296 AC: 7219 AN: 24428

Middle Eastern (MID) AF: 0.242 AC: 480 AN: 1980

European-Non Finnish (NFE) AF: 0.261 AC: 94585 AN: 361970

Other (OTH) AF: 0.228 AC: 6217 AN: 27248

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

African (AFR) AF: 0.0734 AC: 3051 AN: 41546

American (AMR) AF: 0.166 AC: 2540 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3466

East Asian (EAS) AF: 0.146 AC: 757 AN: 5188

South Asian (SAS) AF: 0.175 AC: 844 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3133 AN: 10560

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17345 AN: 67962

Other (OTH) AF: 0.205 AC: 434 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-0.60
PromoterAI		-0.00030	Neutral
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: rs10488682; hg19: chr11-18062482;