rs1386483

Variant names:

• chr12-72018714-T-C
• rs1386483
• NM_173353.4:c.1069-3685T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-72018714-T-C
• chr12-72018714-T-G

Variant summary

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

The NM_173353.4(TPH2):​c.1069-3685T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,970 control chromosomes in the GnomAD database, including 22,437 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 0.53 (22437 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 35 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-3685T>C		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-3685T>C		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80051 AN: 151852 Hom.: 22429 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.527 AC: 80092 AN: 151970 Hom.: 22437 Cov.: 32 AF XY: 0.522 AC XY: 38791 AN XY: 74246

African (AFR) AF: 0.337 AC: 13952 AN: 41440

American (AMR) AF: 0.547 AC: 8355 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2467 AN: 5158

South Asian (SAS) AF: 0.519 AC: 2500 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5369 AN: 10544

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43371 AN: 67952

Other (OTH) AF: 0.558 AC: 1180 AN: 2116

Alfa AF: 0.601 Hom.: 89229

Bravo AF: 0.522

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.69
PhyloP100		-0.32
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: rs1386483; hg19: chr12-72412494;