NM_031448.6(C19orf12):c.161-2del AND Hereditary spastic paraplegia 43

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 27, 2022
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:: RCV002527210.3

Allele description [Variation Report for NM_031448.6(C19orf12):c.161-2del]

NM_031448.6(C19orf12):c.161-2del

Gene:

C19orf12:chromosome 19 open reading frame 12 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19q12

Genomic location:

Preferred name:

NM_031448.6(C19orf12):c.161-2del

HGVS:

NC_000019.10:g.29702979del
NG_031970.2:g.17811del
NM_001031726.4:c.161-2del
NM_001256046.3:c.161-2del
NM_001256047.2:c.161-2del
NM_001282929.1:c.-32-2del
NM_001282930.3:c.-32-2del
NM_001282931.3:c.-32-2del
NM_031448.6:c.161-2delMANE SELECT
NC_000019.9:g.30193886del
NM_001031726.2:c.194-2del

Links:

dbSNP: rs1352744778

NCBI 1000 Genomes Browser:

rs1352744778

Molecular consequence:

NM_001031726.4:c.161-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001256046.3:c.161-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001256047.2:c.161-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282929.1:c.-32-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282930.3:c.-32-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282931.3:c.-32-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_031448.6:c.161-2del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Hereditary spastic paraplegia 43
Synonyms:: Spastic paraplegia 43, autosomal recessive
Identifiers:: MONDO: MONDO:0014024; MedGen: C2680446; Orphanet: 320370; OMIM: 615043

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003472698	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 27, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17576681, 9536098, 23269600, 29915382, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003472698

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 27, 2022)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003472698.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 434550). This variant has been observed in individuals with clinical features of autosomal recessive neurodegeneration with brain iron accumulation (PMID: 23269600, 29915382). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change falls in intron 2 of the C19orf12 gene. It does not directly change the encoded amino acid sequence of the C19orf12 protein. It affects a nucleotide within the consensus splice site.

#	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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