rs1386497

Variant names:

• chr12-71998510-C-A
• rs1386497
• NM_173353.4:c.1068+3945C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-71998510-C-A
• chr12-71998510-C-G
• chr12-71998510-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.1068+3945C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 151,684 control chromosomes in the GnomAD database, including 52,911 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 0.83 (52911 hom., cov: 28)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 16 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1068+3945C>A		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1068+3945C>A		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126484 AN: 151566 Hom.: 52861 Cov.: 28

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.835 AC: 126593 AN: 151684 Hom.: 52911 Cov.: 28 AF XY: 0.837 AC XY: 61975 AN XY: 74086

African (AFR) AF: 0.806 AC: 33340 AN: 41350

American (AMR) AF: 0.875 AC: 13319 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2918 AN: 3466

East Asian (EAS) AF: 0.956 AC: 4923 AN: 5150

South Asian (SAS) AF: 0.882 AC: 4229 AN: 4794

European-Finnish (FIN) AF: 0.816 AC: 8543 AN: 10470

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56474 AN: 67926

Other (OTH) AF: 0.842 AC: 1771 AN: 2104

Alfa AF: 0.834 Hom.: 24849

Bravo AF: 0.838

Asia WGS AF: 0.907 AC: 3153 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.18
PhyloP100		-0.56
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: rs1386497; hg19: chr12-72392290;