11-18019036-T-C

Position:

• chr11-18019036-T-C

Variant summary

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

The NM_004179.3(TPH1):​c.*1955A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,180 control chromosomes in the GnomAD database, including 2,810 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 (2810 hom., cov: 33)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: TPH1 NM_004179.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721

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]

ENSG00000255448 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH1	NM_004179.3	c.*1955A>G		3_prime_UTR_variant	11/11	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019	c.*1955A>G		3_prime_UTR_variant	11/11		NM_004179.3	ENSP00000508368.1
TPH1	ENST00000250018	c.*1955A>G		3_prime_UTR_variant	10/10	1		ENSP00000250018.2
ENSG00000255448	ENST00000525523.1	n.285+1979A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28430 AN: 152050 Hom.: 2802 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.187 AC: 28474 AN: 152170 Hom.: 2810 Cov.: 33 AF XY: 0.192 AC XY: 14263 AN XY: 74408

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.176

Alfa AF: 0.180 Hom.: 569

Bravo AF: 0.189

Asia WGS AF: 0.267 AC: 911 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.88

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: rs8176799; hg19: chr11-18040583;