rs4430554

Variant names:

• chr12-72021078-T-A
• rs4430554
• NM_173353.4:c.1069-1321T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-72021078-T-A
• chr12-72021078-T-C
• chr12-72021078-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.1069-1321T>A 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 152,006 control chromosomes in the GnomAD database, including 22,420 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 (22420 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 2 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=-0.69).
• 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.1069-1321T>A		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.1069-1321T>A		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80069 AN: 151888 Hom.: 22412 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: 0.561

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

GnomAD4 genome AF: 0.527 AC: 80110 AN: 152006 Hom.: 22420 Cov.: 32 AF XY: 0.522 AC XY: 38810 AN XY: 74294

African (AFR) AF: 0.337 AC: 13982 AN: 41456

American (AMR) AF: 0.547 AC: 8349 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2110 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2475 AN: 5174

South Asian (SAS) AF: 0.519 AC: 2500 AN: 4816

European-Finnish (FIN) AF: 0.509 AC: 5367 AN: 10540

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

European-Non Finnish (NFE) AF: 0.638 AC: 43363 AN: 67972

Other (OTH) AF: 0.558 AC: 1179 AN: 2112

Alfa AF: 0.574 Hom.: 3249

Bravo AF: 0.522

Asia WGS AF: 0.477 AC: 1659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.0
DANN	Benign	0.74
PhyloP100		0.46
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: rs4430554; hg19: chr12-72414858;