12-71974791-T-G

Variant names:

• chr12-71974791-T-G
• rs7300641
• NM_173353.4:c.805+2076T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173353.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.805+2076T>G		intron	N/A	NP_775489.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.805+2076T>G		intron	N/A	ENSP00000329093.3

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

African (AFR) AF: 0.621 AC: 25722 AN: 41436

American (AMR) AF: 0.769 AC: 11745 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2908 AN: 3466

East Asian (EAS) AF: 0.814 AC: 4206 AN: 5170

South Asian (SAS) AF: 0.733 AC: 3530 AN: 4816

European-Finnish (FIN) AF: 0.779 AC: 8236 AN: 10566

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55744 AN: 67994

Other (OTH) AF: 0.775 AC: 1638 AN: 2114

Alfa AF: 0.799 Hom.: 153877

Bravo AF: 0.751

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.4
DANN	Benign	0.48
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7300641; hg19: chr12-72368571;