12-71942732-A-G

Position:

• chr12-71942732-A-G

Variant summary

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

The NM_173353.4(TPH2):​c.255+999A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,118 control chromosomes in the GnomAD database, including 13,731 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 0.40 (13731 hom., cov: 33)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.255+999A>G		intron_variant		ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.397+999A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.255+999A>G		intron_variant		1	NM_173353.4	ENSP00000329093	P1
TPH2	ENST00000546576.1	n.265+999A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60677 AN: 152000 Hom.: 13728 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.399 AC: 60693 AN: 152118 Hom.: 13731 Cov.: 33 AF XY: 0.404 AC XY: 30013 AN XY: 74380

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.439

Alfa AF: 0.422 Hom.: 2697

Bravo AF: 0.387

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.38

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: rs10784941; hg19: chr12-72336512;