rs2245360

Positions:

• chr12-102840766-G-A

Variant summary

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

The NM_000277.3(PAH):​c.1200-251C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,920 control chromosomes in the GnomAD database, including 7,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7658 hom., cov: 31)
• Consequence: PAH NM_000277.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.230

Genes affected

PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-102840766-G-A is Benign according to our data. Variant chr12-102840766-G-A is described in ClinVar as [Benign]. Clinvar id is 1183586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAH	NM_000277.3	c.1200-251C>T		intron_variant		ENST00000553106.6
PAH	NM_001354304.2	c.1200-251C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAH	ENST00000553106.6	c.1200-251C>T		intron_variant		1	NM_000277.3	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45854 AN: 151804 Hom.: 7653 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.302 AC: 45871 AN: 151920 Hom.: 7658 Cov.: 31 AF XY: 0.305 AC XY: 22621 AN XY: 74238

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.321

Alfa AF: 0.355 Hom.: 13604

Bravo AF: 0.283

Asia WGS AF: 0.209 AC: 726 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

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.54

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: rs2245360; hg19: chr12-103234544;