NM_000463.3(UGT1A1):c.1043del (p.Asn348fs) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 13, 2023
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:: RCV001817750.6

Allele description [Variation Report for NM_000463.3(UGT1A1):c.1043del (p.Asn348fs)]

NM_000463.3(UGT1A1):c.1043del (p.Asn348fs)

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:

Deletion

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000463.3(UGT1A1):c.1043del (p.Asn348fs)

HGVS:

NC_000002.12:g.233767895del
NG_002601.2:g.183152del
NG_033238.1:g.12623del
NM_000463.3:c.1043delMANE SELECT
NM_001072.4:c.1040delMANE SELECT
NM_007120.3:c.1046delMANE SELECT
NM_019075.4:c.1034delMANE SELECT
NM_019076.5:c.1034delMANE SELECT
NM_019077.3:c.1034delMANE SELECT
NM_019078.2:c.1046delMANE SELECT
NM_019093.4:c.1046delMANE SELECT
NM_021027.3:c.1034delMANE SELECT
NM_205862.3:c.239del
NP_000454.1:p.Asn348Thrfs
NP_000454.1:p.Asn348fs
NP_001063.2:p.Asn347Thrfs
NP_001063.2:p.Asn347fs
NP_009051.1:p.Asn349Thrfs
NP_009051.1:p.Asn349fs
NP_061948.1:p.Asn345Thrfs
NP_061948.1:p.Asn345fs
NP_061949.3:p.Asn345Thrfs
NP_061949.3:p.Asn345fs
NP_061950.2:p.Asn345Thrfs
NP_061950.2:p.Asn345fs
NP_061951.1:p.Asn349Thrfs
NP_061951.1:p.Asn349fs
NP_061966.1:p.Asn349Thrfs
NP_061966.1:p.Asn349fs
NP_066307.1:p.Asn345Thrfs
NP_066307.1:p.Asn345fs
NP_995584.1:p.Asn80Thrfs
NP_995584.1:p.Asn80fs
LRG_733t1:c.1043del
LRG_733:g.12623del
NC_000002.11:g.234676540del
NC_000002.11:g.234676541del
NM_000463.2:c.1043del
NM_000463.2:c.1043delA
NM_001072.3:c.1040delA
NM_007120.2:c.1046delA
NM_019075.2:c.1034delA
NM_019076.4:c.1034delA
NM_019077.2:c.1034delA
NM_019078.1:c.1046delA
NM_019093.2:c.1046delA
NM_021027.2:c.1034delA
NM_205862.1:c.239delA

Protein change:

N345fs

Links:

dbSNP: rs745655794

NCBI 1000 Genomes Browser:

rs745655794

Molecular consequence:

NM_000463.3:c.1043del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001072.4:c.1040del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_007120.3:c.1046del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_019075.4:c.1034del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_019076.5:c.1034del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_019077.3:c.1034del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_019078.2:c.1046del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_019093.4:c.1046del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_021027.3:c.1034del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_205862.3:c.239del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002069122	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 26, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004292174	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23290513, 11013440, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002069122

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 26, 2018)

germline

clinical testing

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

SCV004292174

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 13, 2023)

germline

clinical testing

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

Help

Summary from all submissions

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

UGT1A1 genetic analysis as a diagnostic aid for individuals with unconjugated hyperbilirubinemia.

Skierka JM, Kotzer KE, Lagerstedt SA, O'Kane DJ, Baudhuin LM.

J Pediatr. 2013 Jun;162(6):1146-52, 1152.e1-2. doi: 10.1016/j.jpeds.2012.11.042. Epub 2013 Jan 4.

PubMed [citation]

PMID:: 23290513

See all PubMed Citations (4)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002069122.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292174.1

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

Description

This variant is present in population databases (rs745655794, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Asn348Thrfs*18) in the UGT1A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UGT1A1 are known to be pathogenic (PMID: 23290513). This premature translational stop signal has been observed in individual(s) with Crigler-Najjar syndrome type 1 (PMID: 11013440). This variant is also known as c.1046delA. ClinVar contains an entry for this variant (Variation ID: 1338379). For these reasons, this variant has been classified as Pathogenic.

#	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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