11-18019049-T-C

Variant names:

• chr11-18019049-T-C
• rs2108977
• NM_004179.3:c.*1942A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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]

ENSG00000255448 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TPH1	NM_004179.3	c.*1942A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000682019.1	NP_004170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1	c.*1942A>G		3_prime_UTR_variant	Exon 11 of 11		NM_004179.3	ENSP00000508368.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 6 AN: 12

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.247 AC: 10239 AN: 41478

American (AMR) AF: 0.537 AC: 8199 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2328 AN: 3468

East Asian (EAS) AF: 0.568 AC: 2939 AN: 5178

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4816

European-Finnish (FIN) AF: 0.548 AC: 5780 AN: 10554

Middle Eastern (MID) AF: 0.679 AC: 197 AN: 290

European-Non Finnish (NFE) AF: 0.571 AC: 38820 AN: 67958

Other (OTH) AF: 0.501 AC: 1055 AN: 2106

Alfa AF: 0.505 Hom.: 4954

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
PhyloP100		-0.54
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: rs2108977; hg19: chr11-18040596;