U.S. flag

An official website of the United States government

NM_000026.4(ADSL):c.1337C>A (p.Pro446His) AND Adenylosuccinate lyase deficiency

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Feb 3, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000785042.7

Allele description [Variation Report for NM_000026.4(ADSL):c.1337C>A (p.Pro446His)]

NM_000026.4(ADSL):c.1337C>A (p.Pro446His)

Gene:
ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.1
Genomic location:
Preferred name:
NM_000026.4(ADSL):c.1337C>A (p.Pro446His)
HGVS:
  • NC_000022.11:g.40365025C>A
  • NG_007993.2:g.23526C>A
  • NM_000026.4:c.1337C>AMANE SELECT
  • NM_001123378.3:c.1191+660C>A
  • NM_001317923.2:c.1145C>A
  • NM_001363840.3:c.1337C>A
  • NP_000017.1:p.Pro446His
  • NP_001304852.1:p.Pro382His
  • NP_001350769.1:p.Pro446His
  • NC_000022.10:g.40761029C>A
  • NM_000026.2:c.1337C>A
  • NM_000026.3:c.1337C>A
  • NR_134256.2:n.1427C>A
Protein change:
P382H
Links:
dbSNP: rs755964863
NCBI 1000 Genomes Browser:
rs755964863
Molecular consequence:
  • NM_001123378.3:c.1191+660C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000026.4:c.1337C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001317923.2:c.1145C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363840.3:c.1337C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_134256.2:n.1427C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Adenylosuccinate lyase deficiency (ADSLD)
Identifiers:
MONDO: MONDO:0007068; MedGen: C0268126; Orphanet: 46; OMIM: 103050

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000923595Genomic Research Center, Shahid Beheshti University of Medical Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jan 1, 2019)
unknownclinical testing

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

SCV001205346Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Feb 3, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownno1not providednot providednot providednot providedclinical 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Genomic Research Center, Shahid Beheshti University of Medical Sciences, SCV000923595.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnonot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001205346.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 446 of the ADSL protein (p.Pro446His). This variant is present in population databases (rs755964863, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ADSL-related conditions. ClinVar contains an entry for this variant (Variation ID: 451308). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADSL protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024