11-112269609-T-C

Position:

• chr11-112269609-T-C

Variant summary

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

The ENST00000531673.5(PTS):​c.*416T>C variant causes a 3 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,026 control chromosomes in the GnomAD database, including 35,719 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 0.68 (35716 hom., cov: 31)
  • Exomes 𝑓: 0.80 (3 hom.)
• Consequence: PTS ENST00000531673.5 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 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
PTS	ENST00000531673.5	c.*416T>C		3_prime_UTR_variant, NMD_transcript_variant	7/7	1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103518 AN: 151898 Hom.: 35676 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.696

GnomAD4 exome AF: 0.800 AC: 8 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.750 AC XY: 6 AN XY: 8

Gnomad4 NFE exome AF: 0.800

GnomAD4 genome AF: 0.682 AC: 103618 AN: 152016 Hom.: 35716 Cov.: 31 AF XY: 0.683 AC XY: 50754 AN XY: 74308

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.706

Gnomad4 OTH AF: 0.698

Alfa AF: 0.704 Hom.: 35312

Bravo AF: 0.683

Asia WGS AF: 0.774 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2853127; hg19: chr11-112140332;