12-72058261-C-T

Variant names:

• chr12-72058261-C-T
• rs1352252
• ENST00000547278.1:n.240+10604C>T

Variant summary

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

The ENST00000547278.1(TPH2):​n.240+10604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,984 control chromosomes in the GnomAD database, including 21,559 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 0.51 (21559 hom., cov: 32)
• Consequence: TPH2 ENST00000547278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000547278.1	n.240+10604C>T		intron_variant	Intron 3 of 5	3
TPH2	ENST00000547348.5	n.202+10604C>T		intron_variant	Intron 2 of 3	3
TPH2	ENST00000550403.5	n.121-15332C>T		intron_variant	Intron 1 of 5	3
TPH2	ENST00000551074.5	n.195+10604C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77675 AN: 151866 Hom.: 21547 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.511 AC: 77717 AN: 151984 Hom.: 21559 Cov.: 32 AF XY: 0.515 AC XY: 38242 AN XY: 74284

African (AFR) AF: 0.279 AC: 11579 AN: 41448

American (AMR) AF: 0.559 AC: 8526 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1911 AN: 3472

East Asian (EAS) AF: 0.579 AC: 2984 AN: 5150

South Asian (SAS) AF: 0.547 AC: 2637 AN: 4822

European-Finnish (FIN) AF: 0.611 AC: 6452 AN: 10558

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.616 AC: 41865 AN: 67962

Other (OTH) AF: 0.527 AC: 1111 AN: 2108

Alfa AF: 0.579 Hom.: 5391

Bravo AF: 0.493

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		-0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1352252; hg19: chr12-72452041;