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NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs) AND Crigler-Najjar syndrome type 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 5, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001509551.2

Allele description [Variation Report for NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)]

NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)

Genes:
  • UGT1A:UDP glucuronosyltransferase family 1 member A complex locus [Gene - HGNC]
  • UGT1A10:UDP glucuronosyltransferase family 1 member A10 [Gene - OMIM - HGNC]
  • UGT1A1:UDP glucuronosyltransferase family 1 member A1 [Gene - OMIM - HGNC]
  • UGT1A3:UDP glucuronosyltransferase family 1 member A3 [Gene - OMIM - HGNC]
  • UGT1A4:UDP glucuronosyltransferase family 1 member A4 [Gene - OMIM - HGNC]
  • UGT1A5:UDP glucuronosyltransferase family 1 member A5 [Gene - OMIM - HGNC]
  • UGT1A6:UDP glucuronosyltransferase family 1 member A6 [Gene - OMIM - HGNC]
  • UGT1A7:UDP glucuronosyltransferase family 1 member A7 [Gene - OMIM - HGNC]
  • UGT1A8:UDP glucuronosyltransferase family 1 member A8 [Gene - OMIM - HGNC]
  • UGT1A9:UDP glucuronosyltransferase family 1 member A9 [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
2q37.1
Genomic location:
Preferred name:
NM_000463.3(UGT1A1):c.380_381insGG (p.Cys127fs)
HGVS:
  • NC_000002.12:g.233760667_233760668insGG
  • NG_002601.2:g.175924_175925insGG
  • NG_033238.1:g.5395_5396insGG
  • NM_000463.3:c.380_381insGGMANE SELECT
  • NM_001072.4:c.862-6367_862-6366insGGMANE SELECT
  • NM_007120.3:c.868-6367_868-6366insGGMANE SELECT
  • NM_019075.4:c.856-6367_856-6366insGGMANE SELECT
  • NM_019076.5:c.856-6367_856-6366insGGMANE SELECT
  • NM_019077.3:c.856-6367_856-6366insGGMANE SELECT
  • NM_019078.2:c.868-6367_868-6366insGGMANE SELECT
  • NM_019093.4:c.868-6367_868-6366insGGMANE SELECT
  • NM_021027.3:c.856-6367_856-6366insGGMANE SELECT
  • NM_205862.3:c.61-6367_61-6366insGG
  • NP_000454.1:p.Cys127Trpfs
  • NP_000454.1:p.Cys127fs
  • LRG_733t1:c.380_381insGG
  • LRG_733:g.5395_5396insGG
  • LRG_733p1:p.Cys127Trpfs
  • NC_000002.11:g.234669313_234669314insGG
  • NM_000463.2:c.380_381insGG
Protein change:
C127fs
Links:
dbSNP: rs2125987009
NCBI 1000 Genomes Browser:
rs2125987009
Molecular consequence:
  • NM_000463.3:c.380_381insGG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001072.4:c.862-6367_862-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007120.3:c.868-6367_868-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019075.4:c.856-6367_856-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019076.5:c.856-6367_856-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019077.3:c.856-6367_856-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019078.2:c.868-6367_868-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019093.4:c.868-6367_868-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_021027.3:c.856-6367_856-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
  • NM_205862.3:c.61-6367_61-6366insGG - intron variant - [Sequence Ontology: SO:0001627]
Functional consequence:
protein truncation [Variation Ontology: 0015]

Condition(s)

Name:
Crigler-Najjar syndrome type 1
Synonyms:
HYPERBILIRUBINEMIA, CRIGLER-NAJJAR TYPE I
Identifiers:
MONDO: MONDO:0021020; MedGen: C0010324; OMIM: 218800

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001653677Neonatal Research Center, Shiraz University of Medical Science
no assertion criteria provided
Pathogenic
(Feb 5, 2021) 		germlineresearch

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedresearch

Details of each submission

From Neonatal Research Center, Shiraz University of Medical Science, SCV001653677.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedresearchnot provided

Description

The c.379_380insGG; p.C127fs variant is a null variant (frameshift) in the UGT1A1 gene. Loss-of-function mutation is a known mechanism of Crigler–Najjar syndrome type I (CNS-1). This variant is assumed de novo, but without confirmation of paternity and maternity. Cosegregation with CNS-1 disease in multiple affected family members in a gene definitively known to cause the disease. We identified a novel frameshift insertion mutation (c.379_380insGG; p.C127fs) in the first exon of the UGT1A1 gene in a 16 months old boy. The patient is the offspring of first-cousin couples. Proband has an affected 11 years old brother that previously treated using liver transplantation. We studied the brother of the proband and identified this mutation as a cause of CNS-1 in his brother. However, there was no affected individual in the three-generation pedigree. The protein structure homology model showed that the c.379_380insGG disrupt the reading frame and result in a truncated protein formation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 1, 2024