rs1386496

Variant names:

• chr12-71957010-G-A
• rs1386496
• NM_173353.4:c.608+7355G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-71957010-G-A
• chr12-71957010-G-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.608+7355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,162 control chromosomes in the GnomAD database, including 51,160 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 0.82 (51160 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.608+7355G>A		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.751-4543G>A		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.608+7355G>A		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.619-4543G>A		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.817 AC: 124184 AN: 152044 Hom.: 51125 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.817 AC: 124270 AN: 152162 Hom.: 51160 Cov.: 32 AF XY: 0.820 AC XY: 60969 AN XY: 74378

African (AFR) AF: 0.709 AC: 29420 AN: 41482

American (AMR) AF: 0.869 AC: 13280 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3472

East Asian (EAS) AF: 0.958 AC: 4957 AN: 5174

South Asian (SAS) AF: 0.910 AC: 4395 AN: 4828

European-Finnish (FIN) AF: 0.825 AC: 8730 AN: 10588

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57618 AN: 68016

Other (OTH) AF: 0.837 AC: 1767 AN: 2112

Alfa AF: 0.844 Hom.: 27712

Bravo AF: 0.814

Asia WGS AF: 0.915 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.36
PhyloP100		-1.0
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: rs1386496; hg19: chr12-72350790;