NM_000277.3(PAH):c.284_285delinsCA (p.Ile95Thr) AND PAH-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 13, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003390792.4

Allele description [Variation Report for NM_000277.3(PAH):c.284_285delinsCA (p.Ile95Thr)]

NM_000277.3(PAH):c.284_285delinsCA (p.Ile95Thr)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.284_285delinsCA (p.Ile95Thr)

HGVS:

NC_000012.12:g.102894802_102894803delinsTG
NG_008690.2:g.68608_68609delinsCA
NM_000277.3:c.284_285delinsCAMANE SELECT
NM_001354304.2:c.284_285delinsCA
NP_000268.1:p.Ile95Thr
NP_001341233.1:p.Ile95Thr
NC_000012.11:g.103288580_103288581delinsTG
NC_000012.12:g.102894802_102894803delGAinsTG
NM_000277.1:c.284_285delTCinsCA
NM_000277.1:c.284_285delinsCA
NM_000277.2(PAH):c.284_285delTCinsCA
p.Ile95Thr

Protein change:

I95T

Links:

dbSNP: rs281865432

NCBI 1000 Genomes Browser:

rs281865432

Molecular consequence:

NM_000277.3:c.284_285delinsCA - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.284_285delinsCA - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: PAH-related disorder
Synonyms:: PAH-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004112681	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004112681

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 13, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004112681.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The PAH c.284_285delinsCA variant is predicted to result in an in-frame deletion and insertion. which is predicted to result in the amino acid substitution p.Ile95Thr. This variant has been interpreted by the ClinGen PAH Variant Curation Expert Panel as uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/120272/). A different amino acid substitution at this position (p.Ile95Phe) has been reported in several patients with phenylketonuria (Bercovich D et al 2008. PubMed ID: 18299955; Rajabi F et al 2019. PubMed ID: 31623983). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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Relating variation to medicine