rs62509021

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP7

This summary comes from the ClinGen Evidence Repository: The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA229433/MONDO:0009861/006

Frequency

Genomes: 𝑓 0.017 ( 34 hom., cov: 33)
Exomes 𝑓: 0.022 ( 444 hom. )

Consequence

PAH
ENST00000553106.6 intron

Scores

2

Clinical Significance

Benign reviewed by expert panel B:4O:1

Conservation

PhyloP100: -1.87
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP7
For more information check the summary or visit ClinGen Evidence Repository.
BA1
For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAHNM_000277.3 linkuse as main transcriptc.1316-35C>T intron_variant ENST00000553106.6 NP_000268.1
PAHNM_001354304.2 linkuse as main transcriptc.1316-35C>T intron_variant NP_001341233.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAHENST00000553106.6 linkuse as main transcriptc.1316-35C>T intron_variant 1 NM_000277.3 ENSP00000448059 P1

Frequencies

GnomAD3 genomes
AF:
0.0167
AC:
2543
AN:
152168
Hom.:
34
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00461
Gnomad AMI
AF:
0.0197
Gnomad AMR
AF:
0.0207
Gnomad ASJ
AF:
0.0190
Gnomad EAS
AF:
0.000769
Gnomad SAS
AF:
0.0124
Gnomad FIN
AF:
0.0101
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0255
Gnomad OTH
AF:
0.0196
GnomAD3 exomes
AF:
0.0161
AC:
4031
AN:
250524
Hom.:
53
AF XY:
0.0168
AC XY:
2283
AN XY:
135492
show subpopulations
Gnomad AFR exome
AF:
0.00329
Gnomad AMR exome
AF:
0.0130
Gnomad ASJ exome
AF:
0.0189
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0139
Gnomad FIN exome
AF:
0.00977
Gnomad NFE exome
AF:
0.0229
Gnomad OTH exome
AF:
0.0182
GnomAD4 exome
AF:
0.0223
AC:
32486
AN:
1455256
Hom.:
444
Cov.:
28
AF XY:
0.0222
AC XY:
16076
AN XY:
724472
show subpopulations
Gnomad4 AFR exome
AF:
0.00354
Gnomad4 AMR exome
AF:
0.0145
Gnomad4 ASJ exome
AF:
0.0160
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0136
Gnomad4 FIN exome
AF:
0.00974
Gnomad4 NFE exome
AF:
0.0254
Gnomad4 OTH exome
AF:
0.0232
GnomAD4 genome
AF:
0.0167
AC:
2542
AN:
152286
Hom.:
34
Cov.:
33
AF XY:
0.0156
AC XY:
1163
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00460
Gnomad4 AMR
AF:
0.0207
Gnomad4 ASJ
AF:
0.0190
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.0126
Gnomad4 FIN
AF:
0.0101
Gnomad4 NFE
AF:
0.0255
Gnomad4 OTH
AF:
0.0194
Alfa
AF:
0.0218
Hom.:
9
Bravo
AF:
0.0165
Asia WGS
AF:
0.00549
AC:
19
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4Other:1
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

not provided Benign:2Other:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
not provided, no classification providedliterature onlyDeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE-- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Phenylketonuria Benign:1
Benign, reviewed by expert panelcurationClinGen PAH Variant Curation Expert PanelMar 27, 2020The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.046
DANN
Benign
0.20

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62509021; hg19: chr12-103233031; API