rs7963720

Variant names:

• chr12-71972406-C-G
• rs7963720
• NM_173353.4:c.609-113C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-71972406-C-G
• chr12-71972406-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173353.4(TPH2):​c.609-113C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 968,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.609-113C>G		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.609-113C>G		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151990 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000135 AC: 11 AN: 816630 Hom.: 0 AF XY: 0.00000464 AC XY: 2 AN XY: 430576

African (AFR) AF: 0.00 AC: 0 AN: 20976

American (AMR) AF: 0.00 AC: 0 AN: 43624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22058

East Asian (EAS) AF: 0.00 AC: 0 AN: 36722

South Asian (SAS) AF: 0.00 AC: 0 AN: 72616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.0000209 AC: 11 AN: 525348

Other (OTH) AF: 0.00 AC: 0 AN: 39036

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151990 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00000246 Hom.: 63991

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.016
DANN	Benign	0.55
PhyloP100		-2.1

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: rs7963720; hg19: chr12-72366186;