NM_031448.6(C19orf12):c.161-2del AND Neurodegeneration with brain iron accumulation 4

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Sep 1, 2022
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:: RCV000503280.7

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]

Observations:

Condition(s)

Name:: Neurodegeneration with brain iron accumulation 4 (NBIA4)
Synonyms:: MITOCHONDRIAL PROTEIN-ASSOCIATED NEURODEGENERATION
Identifiers:: MONDO: MONDO:0013674; MedGen: C3280371; Orphanet: 289560; OMIM: 614298

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
SCV000593800	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 26, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002573259	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29915382, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000593800

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 26, 2016)

germline

clinical testing

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

SCV002573259

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 1, 2022)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.

Sun M, Johnson AK, Nelakuditi V, Guidugli L, Fischer D, Arndt K, Ma L, Sandford E, Shakkottai V, Boycott K, Warman-Chardon J, Li Z, Del Gaudio D, Burmeister M, Gomez CM, Waggoner DJ, Das S.

Genet Med. 2019 Jan;21(1):195-206. doi: 10.1038/s41436-018-0007-7. Epub 2018 Jun 18.

PubMed [citation]

PMID:: 29915382
PMCID:: PMC6524765

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 Genetic Services Laboratory, University of Chicago, SCV000593800.1

#	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 3billion, SCV002573259.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Canonical splice site is predicted to alter splicing and result in a loss or disruption of normal protein function. The predicted truncated protein may be shortened by more than 10%. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with C19orf12-related disorder (ClinVar ID: VCV000434550 / PMID: 29915382). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine