chr12-72016512-C-A

Position:

• chr12-72016512-C-A

Variant summary

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

The NM_173353.4(TPH2):​c.1069-5887C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,816 control chromosomes in the GnomAD database, including 37,837 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 0.70 (37837 hom., cov: 30)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.1069-5887C>A		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-5887C>A		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 106903 AN: 151696 Hom.: 37791 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.705 AC: 107013 AN: 151816 Hom.: 37837 Cov.: 30 AF XY: 0.702 AC XY: 52054 AN XY: 74180

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.700

Alfa AF: 0.713 Hom.: 55136

Bravo AF: 0.710

Asia WGS AF: 0.635 AC: 2210 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.50

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: rs1487275; hg19: chr12-72410292;