rs1386488

Variant names:

• chr12-71950838-C-A
• rs1386488
• NM_173353.4:c.608+1183C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-71950838-C-A
• chr12-71950838-C-G
• chr12-71950838-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.608+1183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 151,964 control chromosomes in the GnomAD database, including 48,325 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 0.80 (48325 hom., cov: 30)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.608+1183C>A		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.750+1183C>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.608+1183C>A		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.618+1183C>A		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 120978 AN: 151846 Hom.: 48278 Cov.: 30

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.811

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.797 AC: 121080 AN: 151964 Hom.: 48325 Cov.: 30 AF XY: 0.798 AC XY: 59267 AN XY: 74276

African (AFR) AF: 0.739 AC: 30599 AN: 41422

American (AMR) AF: 0.833 AC: 12719 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2938 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4329 AN: 5152

South Asian (SAS) AF: 0.776 AC: 3726 AN: 4804

European-Finnish (FIN) AF: 0.808 AC: 8539 AN: 10562

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55469 AN: 67968

Other (OTH) AF: 0.809 AC: 1704 AN: 2106

Alfa AF: 0.811 Hom.: 194148

Bravo AF: 0.797

Asia WGS AF: 0.752 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.66
DANN	Benign	0.57
PhyloP100		-0.066
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: rs1386488; hg19: chr12-72344618;