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NM_000404.4(GLB1):c.65_75+1del AND Infantile GM1 gangliosidosis

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 13, 2021
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:
RCV003155274.3

Allele description [Variation Report for NM_000404.4(GLB1):c.65_75+1del]

NM_000404.4(GLB1):c.65_75+1del

Genes:
LOC129936434:ATAC-STARR-seq lymphoblastoid silent region 14182 [Gene]
GLB1:galactosidase beta 1 [Gene - OMIM - HGNC]
TMPPE:transmembrane protein with metallophosphoesterase domain [Gene - HGNC]
Variant type:
Deletion
Cytogenetic location:
3p22.3
Genomic location:
Preferred name:
NM_000404.4(GLB1):c.65_75+1del
Other names:
p.Arg22_Asn26delinsGLn
HGVS:
  • NC_000003.12:g.33097010_33097021del
  • NG_009005.1:g.5182_5193del
  • NG_009005.2:g.5125_5136del
  • NG_169445.1:g.377_388del
  • NM_000404.4:c.65_75+1delMANE SELECT
  • NM_001039770.3:c.-411_-400delMANE SELECT
  • NM_001135602.3:c.65_75+1del
  • NM_001136238.2:c.-307_-296del
  • NM_001317040.2:c.65_75+1del
  • NM_001393580.1:c.65_75+1del
  • NC_000003.11:g.33138502_33138513del
  • NM_000404.2:c.65_75+1del
  • NM_000404.2:c.65_75+1del12
Links:
dbSNP: rs1382394474
NCBI 1000 Genomes Browser:
rs1382394474
Molecular consequence:
  • NM_001039770.3:c.-411_-400del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001136238.2:c.-307_-296del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000404.4:c.65_75+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001135602.3:c.65_75+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001317040.2:c.65_75+1del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001393580.1:c.65_75+1del - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

Condition(s)

Name:
Infantile GM1 gangliosidosis
Synonyms:
Gangliosidosis, Generalized GM1, Type 1; GM1 gangliosidosis type 1; GM1-gangliosidosis, type I; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009260; MedGen: C0268271; Orphanet: 354; OMIM: 230500

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003843882Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 13, 2021) 		germlineclinical testing

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

SCV004047639Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenicgermlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
Hindugermlineyes1not 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

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV003843882.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Hindu1not providednot providedclinical testing PubMed (1)

Description

A homozygous deletion in exon 1/Intron1 of the GLB1 gene that results in the amino acid deletion fron codon 22 to 26 was detected. The observed variant c.65_75+1 (p.Arg22_Asn26delinsGln) has a minor allele frequency of 0.04% gnomAD databases. The in silico prediction of the variant is damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a pathogenic.

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047639.1

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

Description

The splice site c.65_75+1del variant has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in 1000 Genomes and in 0.0004% alleles in heterozygous state in gnomAD. This variant has been reported to the ClinVar database as Likely Pathogenic. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024