12-71983532-G-C

Variant names:

• chr12-71983532-G-C
• rs11179027
• NM_173353.4:c.941+4445G>C

Variant summary

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

The NM_173353.4(TPH2):​c.941+4445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,996 control chromosomes in the GnomAD database, including 5,666 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 0.26 (5666 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.941+4445G>C		intron_variant	Intron 7 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.941+4445G>C		intron_variant	Intron 7 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40201 AN: 151878 Hom.: 5659 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.265 AC: 40240 AN: 151996 Hom.: 5666 Cov.: 31 AF XY: 0.269 AC XY: 19970 AN XY: 74280

African (AFR) AF: 0.200 AC: 8302 AN: 41452

American (AMR) AF: 0.330 AC: 5031 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 843 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2429 AN: 5148

South Asian (SAS) AF: 0.372 AC: 1788 AN: 4808

European-Finnish (FIN) AF: 0.259 AC: 2736 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18229 AN: 67974

Other (OTH) AF: 0.263 AC: 555 AN: 2112

Alfa AF: 0.265 Hom.: 675

Bravo AF: 0.266

Asia WGS AF: 0.415 AC: 1442 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	1.4
DANN	Benign	0.50
PhyloP100		-0.028
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: rs11179027; hg19: chr12-72377312;