12-102884967-C-T

Position:

• chr12-102884967-C-T

Variant summary

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

The NM_000277.3(PAH):​c.353-7417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,042 control chromosomes in the GnomAD database, including 14,806 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 0.43 (14806 hom., cov: 32)
• Consequence: PAH NM_000277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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]

PAH (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAH	NM_000277.3	c.353-7417G>A		intron_variant		ENST00000553106.6	NP_000268.1
PAH	NM_001354304.2	c.353-7417G>A		intron_variant			NP_001341233.1
PAH	XM_017019370.2	c.353-7417G>A		intron_variant			XP_016874859.1
LOC124902999	XR_007063428.1	n.862+5034C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAH	ENST00000553106.6	c.353-7417G>A		intron_variant		1	NM_000277.3	ENSP00000448059.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65932 AN: 151924 Hom.: 14796 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.434 AC: 65969 AN: 152042 Hom.: 14806 Cov.: 32 AF XY: 0.434 AC XY: 32228 AN XY: 74324

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.423

Alfa AF: 0.446 Hom.: 14634

Bravo AF: 0.417

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.39

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: rs1722392; hg19: chr12-103278745;