Genetic Variant PTS:n.*416T>C (chr11-112269609-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000531673.5(PTS):n.*416T>C variant causes a non coding transcript exon 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 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Publications

14 publications found

Variant links:

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]

PTS Gene-Disease associations (from GenCC):

BH4-deficient hyperphenylalaninemia A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

PTS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000531673.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTS	ENST00000531673.5	TSL:1	n.*416T>C		non_coding_transcript_exon	Exon 7 of 7	ENSP00000433469.1	E9PKY8
	PTS	ENST00000531673.5	TSL:1	n.*416T>C		3_prime_UTR	Exon 7 of 7	ENSP00000433469.1	E9PKY8

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103518

AN:

151898

Hom.:

35676

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.750

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.800

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.682

AC:

103618

AN:

152016

Hom.:

35716

Cov.:

AF XY:

0.683

AC XY:

50754

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.583

AC:

24141

AN:

41422

American (AMR)

AF:

0.747

AC:

11420

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2673

AN:

3470

East Asian (EAS)

AF:

0.791

AC:

4089

AN:

5170

South Asian (SAS)

AF:

0.805

AC:

3874

AN:

4814

European-Finnish (FIN)

AF:

0.671

AC:

7096

AN:

10574

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.706

AC:

47981

AN:

67966

Other (OTH)

AF:

0.698

AC:

1478

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1638

3277

4915

6554

8192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.700

Hom.:

46336

Bravo

AF:

0.683

Asia WGS

AF:

0.774

AC:

2690

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

(source)

DANN

Benign

0.30

PhyloP100

-1.1

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over