rs1386493

Variant names:

• chr12-71961399-A-G
• rs1386493
• NM_173353.4:c.609-11120A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-71961399-A-G
• chr12-71961399-A-T

Variant summary

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

The NM_173353.4(TPH2):​c.609-11120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,176 control chromosomes in the GnomAD database, including 47,337 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 0.79 (47337 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.609-11120A>G		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.751-154A>G		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.609-11120A>G		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.619-154A>G		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119615 AN: 152058 Hom.: 47309 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.787 AC: 119687 AN: 152176 Hom.: 47337 Cov.: 32 AF XY: 0.786 AC XY: 58489 AN XY: 74400

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.801

Alfa AF: 0.806 Hom.: 7416

Bravo AF: 0.782

Asia WGS AF: 0.743 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.55

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: rs1386493; hg19: chr12-72355179;