rs10860935

Positions:

• chr12-102889153-T-A

Variant summary

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

The NM_000277.3(PAH):​c.352+5582A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,028 control chromosomes in the GnomAD database, including 3,102 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 0.18 (3102 hom., cov: 31)
• Consequence: PAH NM_000277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

LOC124902999 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAH	NM_000277.3	c.352+5582A>T		intron_variant		ENST00000553106.6	NP_000268.1
LOC124902999	XR_007063428.1	n.862+9220T>A		intron_variant, non_coding_transcript_variant
PAH	NM_001354304.2	c.352+5582A>T		intron_variant			NP_001341233.1
PAH	XM_017019370.2	c.352+5582A>T		intron_variant			XP_016874859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAH	ENST00000553106.6	c.352+5582A>T		intron_variant		1	NM_000277.3	ENSP00000448059	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27724 AN: 151910 Hom.: 3088 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0854

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.183 AC: 27779 AN: 152028 Hom.: 3102 Cov.: 31 AF XY: 0.178 AC XY: 13256 AN XY: 74326

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.0868

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.176

Alfa AF: 0.162 Hom.: 294

Bravo AF: 0.194

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.078
DANN	Benign	0.72

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: rs10860935; hg19: chr12-103282931;