chr12-72018792-T-G

Position:

• chr12-72018792-T-G

Variant summary

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

The NM_173353.4(TPH2):​c.1069-3607T>G 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 152,010 control chromosomes in the GnomAD database, including 22,426 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 (22426 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928

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=-0.77).
• 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/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-3607T>G		intron_variant		ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-3607T>G		intron_variant		1	NM_173353.4	ENSP00000329093	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80047 AN: 151892 Hom.: 22418 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.527 AC: 80088 AN: 152010 Hom.: 22426 Cov.: 32 AF XY: 0.522 AC XY: 38814 AN XY: 74298

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.557

Alfa AF: 0.584 Hom.: 6756

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	-0.77
CADD	Benign	14
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1386482; hg19: chr12-72412572;