12-71974791-T-G

Position:

• chr12-71974791-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.805+2076T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,044 control chromosomes in the GnomAD database, including 43,915 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 0.75 (43915 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.805+2076T>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.805+2076T>G		intron_variant		1	NM_173353.4	ENSP00000329093	P1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114687 AN: 151926 Hom.: 43897 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.755 AC: 114739 AN: 152044 Hom.: 43915 Cov.: 31 AF XY: 0.753 AC XY: 55933 AN XY: 74296

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.820

Gnomad4 OTH AF: 0.775

Alfa AF: 0.810 Hom.: 102835

Bravo AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.48

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: rs7300641; hg19: chr12-72368571;