rs187840760

Variant names:

• chr12-71938899-G-A
• rs187840760
• NM_173353.4:c.-88G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-71938899-G-A
• chr12-71938899-G-C
• chr12-71938899-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173353.4(TPH2):​c.-88G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 985,434 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: TPH2 NM_173353.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 0 publications found

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic 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 may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.-88G>A		5_prime_UTR_variant	Exon 1 of 11	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.55G>A		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.-88G>A		5_prime_UTR_variant	Exon 1 of 11	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.-78G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000203 AC: 2 AN: 985434 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 511220

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24256

American (AMR) AF: 0.00 AC: 0 AN: 43946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23216

East Asian (EAS) AF: 0.00 AC: 0 AN: 37414

South Asian (SAS) AF: 0.00 AC: 0 AN: 76642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3524

European-Non Finnish (NFE) AF: 0.00000292 AC: 2 AN: 685420

Other (OTH) AF: 0.00 AC: 0 AN: 44708

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.99
DANN	Benign	0.86
PhyloP100		-1.6
PromoterAI		0.029	Neutral

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: rs187840760; hg19: chr12-72332679; COSMIC: COSV100422065; COSMIC: COSV100422065;