NM_000398.7(CYB5R3):c.478C>T (p.Arg160Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 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:: RCV000578723.4

Allele description [Variation Report for NM_000398.7(CYB5R3):c.478C>T (p.Arg160Ter)]

NM_000398.7(CYB5R3):c.478C>T (p.Arg160Ter)

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.478C>T (p.Arg160Ter)

HGVS:

NC_000022.11:g.42627674G>A
NG_012194.1:g.26726C>T
NM_000398.7:c.478C>TMANE SELECT
NM_001129819.2:c.409C>T
NM_001171660.2:c.577C>T
NM_001171661.1:c.409C>T
NM_007326.4:c.409C>T
NP_000389.1:p.Arg160Ter
NP_001123291.1:p.Arg137Ter
NP_001165131.1:p.Arg193Ter
NP_001165132.1:p.Arg137Ter
NP_015565.1:p.Arg137Ter
NC_000022.10:g.43023680G>A
NM_000398.6:c.478C>T

Protein change:

R137*; ARG160TER

Links:

OMIM: 613213.0015; dbSNP: rs61732609

NCBI 1000 Genomes Browser:

rs61732609

Molecular consequence:

NM_000398.7:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001129819.2:c.409C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171660.2:c.577C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171661.1:c.409C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_007326.4:c.409C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Calidris pugnax cell cycle associated protein 1 (CAPRIN1), transcript...
PREDICTED: Calidris pugnax cell cycle associated protein 1 (CAPRIN1), transcript variant X3, mRNA
gi|960978431|ref|XM_014948843.1|

Nucleotide
PREDICTED: Bactrocera oleae dnaJ homolog subfamily B member 6 (LOC106623636), tr...
PREDICTED: Bactrocera oleae dnaJ homolog subfamily B member 6 (LOC106623636), transcript variant X4, mRNA
gi|1912037983|ref|XM_036369095.1|

Nucleotide
cytochrome c oxidase subunit 7A2, mitochondrial isoform X1 [Rattus norvegicus]
cytochrome c oxidase subunit 7A2, mitochondrial isoform X1 [Rattus norvegicus]
gi|2678963381|ref|XP_063121086.1|

Protein
carnitine O-acetyltransferase isoform X3 [Mus musculus]
carnitine O-acetyltransferase isoform X3 [Mus musculus]
gi|1720396891|ref|XP_030102925.1|

Protein
phosphatidylserine lipase ABHD16A isoform X2 [Rattus norvegicus]
phosphatidylserine lipase ABHD16A isoform X2 [Rattus norvegicus]
gi|2678924611|ref|XP_063135278.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000680519	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 13, 2023)	germline	clinical testing	Citation Link,
SCV004300035	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 20, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10874300, 18318771, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000680519

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 13, 2023)

germline

clinical testing

Citation Link,

SCV004300035

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 20, 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

A case of methemoglobinemia type II due to NADH-cytochrome b5 reductase deficiency: determination of the molecular basis.

Aalfs CM, Salieb-Beugelaar GB, Wanders RJ, Mannens MM, Wijburg FA.

Hum Mutat. 2000;16(1):18-22.

PubMed [citation]

PMID:: 10874300

Recessive congenital methaemoglobinaemia: cytochrome b(5) reductase deficiency.

Percy MJ, Lappin TR.

Br J Haematol. 2008 May;141(3):298-308. doi: 10.1111/j.1365-2141.2008.07017.x. Epub 2008 Mar 3. Review.

PubMed [citation]

PMID:: 18318771

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000680519.3

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate a damaging effect, as variant results in absence of protein due to proteolytic degradation (Davis et al., 2004); This variant is associated with the following publications: (PMID: 23113554, 18318771, 23594618, 29375859, 31898843, 25525159, 15953014, 18202104, 15488472, 10874300)

#	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, SCV004300035.1

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

Description

This premature translational stop signal has been observed in individual(s) with methemoglobinemia type II (PMID: 10874300). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 248). This variant is present in population databases (rs61732609, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg160*) in the CYB5R3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CYB5R3 are known to be pathogenic (PMID: 18318771).

#	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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