chr11-112229960-C-T

Position:

• chr11-112229960-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000317.3(PTS):​c.164-248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 563,132 control chromosomes in the GnomAD database, including 144,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33440 hom., cov: 32)
  • Exomes 𝑓: 0.73 (111211 hom.)
• Consequence: PTS NM_000317.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-112229960-C-T is Benign according to our data. Variant chr11-112229960-C-T is described in ClinVar as [Benign]. Clinvar id is 1258222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTS	NM_000317.3	c.164-248C>T		intron_variant		ENST00000280362.8	NP_000308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTS	ENST00000280362.8	c.164-248C>T		intron_variant		1	NM_000317.3	ENSP00000280362	P1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98311 AN: 151986 Hom.: 33420 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.732 AC: 300867 AN: 411028 Hom.: 111211 AF XY: 0.737 AC XY: 161387 AN XY: 219014

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.753

Gnomad4 ASJ exome AF: 0.780

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.783

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.720

GnomAD4 genome AF: 0.647 AC: 98361 AN: 152104 Hom.: 33440 Cov.: 32 AF XY: 0.650 AC XY: 48332 AN XY: 74366

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.677

Alfa AF: 0.672 Hom.: 4328

Bravo AF: 0.639

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2518352; hg19: chr11-112100683;