11-112265855-T-C

Position:

• chr11-112265855-T-C

Variant summary

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

The ENST00000531673.5(PTS):​c.*364-3702T>C variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,974 control chromosomes in the GnomAD database, including 37,161 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 0.69 (37161 hom., cov: 31)
• Consequence: PTS ENST00000531673.5 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

Genes affected

PTS (HGNC:9689): (6-pyruvoyltetrahydropterin synthase) The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTS	ENST00000531673.5	c.*364-3702T>C		intron_variant, NMD_transcript_variant		1		ENSP00000433469

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105511 AN: 151856 Hom.: 37123 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.695 AC: 105609 AN: 151974 Hom.: 37161 Cov.: 31 AF XY: 0.696 AC XY: 51695 AN XY: 74282

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.802

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.706

Alfa AF: 0.700 Hom.: 4393

Bravo AF: 0.694

Asia WGS AF: 0.767 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs891360; hg19: chr11-112136578;