NM_054012.4(ASS1):c.-4C>T AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 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:: RCV003230438.1

Allele description [Variation Report for NM_054012.4(ASS1):c.-4C>T]

NM_054012.4(ASS1):c.-4C>T

Gene:

ASS1:argininosuccinate synthase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.11

Genomic location:

Preferred name:

NM_054012.4(ASS1):c.-4C>T

HGVS:

NC_000009.12:g.130452225C>T
NG_011542.1:g.12519C>T
NM_000050.4:c.-4C>T
NM_054012.4:c.-4C>TMANE SELECT
NC_000009.11:g.133327612C>T
NM_054012.3:c.-4C>T

Links:

dbSNP: rs138350285

NCBI 1000 Genomes Browser:

rs138350285

Molecular consequence:

NM_000050.4:c.-4C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_054012.4:c.-4C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003928990	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19006241, 28111830, 32778825 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003928990

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 13, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene.

Engel K, Höhne W, Häberle J.

Hum Mutat. 2009 Mar;30(3):300-7. doi: 10.1002/humu.20847. Review.

PubMed [citation]

PMID:: 19006241

Mutations in the Human Argininosuccinate Synthetase (ASS1) Gene, Impact on Patients, Common Changes, and Structural Considerations.

Diez-Fernandez C, Rüfenacht V, Häberle J.

Hum Mutat. 2017 May;38(5):471-484. doi: 10.1002/humu.23184. Epub 2017 Feb 15. Review.

PubMed [citation]

PMID:: 28111830

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003928990.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: ASS1 c.-4C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.00056 in 250834 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in ASS1 causing Citrullinemia Type I (0.00056 vs 0.0041), allowing no conclusion about variant significance. The variant was reported in the literature without strong evidence for causality. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified as VUS (n=5), Likely Pathogenic (n=1) and Likely Benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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

ClinVar

Relating variation to medicine