rs41317114

chr12-72032569-G-C

Variant summary

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

The ENST00000547278.1(TPH2):n.78+1178G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 151,966 control chromosomes in the GnomAD database, including 955 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 0.089 (955 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: TPH2 ENST00000547278.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000547278.1	n.78+1178G>C		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000547348.5	n.100+1178G>C		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000550403.5	n.120+1178G>C		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000551074.5	n.93+1178G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13420 AN: 151824 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0556

GnomAD4 genome AF: 0.0885 AC: 13450 AN: 151942 Hom.: 955 Cov.: 32 AF XY: 0.0873 AC XY: 6482 AN XY: 74288

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.0662 Hom.: 61

Bravo AF: 0.0958

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.1
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41317114; hg19: chr12-72426349;