12-72058261-C-T

Position:

• chr12-72058261-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000547278.1(TPH2):​n.240+10604C>T variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000547278.1	n.240+10604C>T		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000547348.5	n.202+10604C>T		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000550403.5	n.121-15332C>T		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000551074.5	n.195+10604C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.527

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1352252; hg19: chr12-72452041;