NM_000398.7(CYB5R3):c.464-2A>C AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 5, 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:: RCV001390260.5

Allele description

NM_000398.7(CYB5R3):c.464-2A>C

Gene:

CYB5R3:cytochrome b5 reductase 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.2

Genomic location:

Preferred name:

NM_000398.7(CYB5R3):c.464-2A>C

HGVS:

NC_000022.11:g.42627690T>G
NG_012194.1:g.26710A>C
NM_000398.7:c.464-2A>CMANE SELECT
NM_001129819.2:c.395-2A>C
NM_001171660.2:c.563-2A>C
NM_001171661.1:c.395-2A>C
NM_007326.4:c.395-2A>C
NC_000022.10:g.43023696T>G
NM_000398.6:c.464_547del

Note:

NCBI staff reviewed the sequence information reported in PubMed 9266404 to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS5AS, A-C, -2

Links:

OMIM: 613213.0012; dbSNP: rs794728013

NCBI 1000 Genomes Browser:

rs794728013

Molecular consequence:

NM_000398.7:c.464-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001129819.2:c.395-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001171660.2:c.563-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001171661.1:c.395-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_007326.4:c.395-2A>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV001591936	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 16, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15921385, 16199547, 18318771, 9266404, 28492532
SCV002756852	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 5, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591936

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 16, 2018)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV002756852

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 5, 2022)

germline

clinical testing

Citation Link

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

Heterogeneity of the molecular biology of methemoglobinemia: a study of eight consecutive patients.

Maran J, Guan Y, Ou CN, Prchal JT.

Haematologica. 2005 May;90(5):687-9.

PubMed [citation]

PMID:: 15921385

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001591936.4

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

Description

This variant has been observed in individuals affected with recessive congenital methemoglobinemia (RCM) type II (PMID: 15921385, 9266404). ClinVar contains an entry for this variant (Variation ID: 245). For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYB5R3 are known to be pathogenic (PMID: 18318771). Experimental studies have shown that this intronic change causes aberrant splicing of the CYB5R3 mRNA (PMID: 9266404). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 5 of the CYB5R3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	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

From GeneDx, SCV002756852.1

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

Description

Canonical splice site variant expected to result in aberrant splicing, and in vitro studies demonstrate altered splicing (Maran et al., 2005); This variant is associated with the following publications: (PMID: 31898843, 25525159, 15921385, 15744830, 9266404)

#	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

Last Updated: Feb 14, 2024

ClinVar

Relating variation to medicine