11-18019049-T-C

Position:

• chr11-18019049-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.*1942A>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 0.476 in 152,042 control chromosomes in the GnomAD database, including 18,791 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 0.48 (18788 hom., cov: 32)
  • Exomes 𝑓: 0.57 (3 hom.)
• Consequence: TPH1 NM_004179.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH1	NM_004179.3	c.*1942A>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.*1942A>G		3_prime_UTR_variant	11/11		NM_004179.3	ENSP00000508368.1
TPH1	ENST00000250018	c.*1942A>G		3_prime_UTR_variant	10/10	1		ENSP00000250018.2
ENSG00000255448	ENST00000525523.1	n.285+1966A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72357 AN: 151910 Hom.: 18788 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.505

GnomAD4 exome AF: 0.571 AC: 8 AN: 14 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.476 AC: 72373 AN: 152028 Hom.: 18788 Cov.: 32 AF XY: 0.475 AC XY: 35310 AN XY: 74314

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.501

Alfa AF: 0.514 Hom.: 4506

Bravo AF: 0.465

Asia WGS AF: 0.509 AC: 1740 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.0
DANN	Benign	0.87

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: rs2108977; hg19: chr11-18040596;