rs7485331

Positions:

• chr12-102918841-C-A

Variant summary

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

The NM_001354304.2(PAH):​c.-95-1616G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,924 control chromosomes in the GnomAD database, including 13,687 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 0.40 (13687 hom., cov: 32)
• Consequence: PAH NM_001354304.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAH	NM_001354304.2	c.-95-1616G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAH	ENST00000546844.1	c.-95-1616G>T		intron_variant		3
PAH	ENST00000551337.5	c.-95-1616G>T		intron_variant		3
PAH	ENST00000546708.5	n.493-1616G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61032 AN: 151806 Hom.: 13644 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.402 AC: 61116 AN: 151924 Hom.: 13687 Cov.: 32 AF XY: 0.398 AC XY: 29581 AN XY: 74250

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.381

Alfa AF: 0.352 Hom.: 2066

Bravo AF: 0.432

Asia WGS AF: 0.315 AC: 1096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7485331; hg19: chr12-103312619;