NM_003172.4(SURF1):c.563A>G (p.Asn188Ser) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 1, 2013
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:: RCV000196814.4

Allele description [Variation Report for NM_003172.4(SURF1):c.563A>G (p.Asn188Ser)]

NM_003172.4(SURF1):c.563A>G (p.Asn188Ser)

Gene:

SURF1:SURF1 cytochrome c oxidase assembly factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.2

Genomic location:

Preferred name:

NM_003172.4(SURF1):c.563A>G (p.Asn188Ser)

HGVS:

NC_000009.12:g.133352719T>C
NG_008477.1:g.8788A>G
NM_001280787.1:c.236A>G
NM_003172.4:c.563A>GMANE SELECT
NP_001267716.1:p.Asn79Ser
NP_003163.1:p.Asn188Ser
NC_000009.11:g.136219574T>C
NM_003172.2:c.563A>G
NM_003172.3:c.563A>G
p.N188S

Protein change:

N188S

Links:

dbSNP: rs200702528

NCBI 1000 Genomes Browser:

rs200702528

Molecular consequence:

NM_001280787.1:c.236A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003172.4:c.563A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000252351	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Oct 1, 2013)	germline	clinical testing	Citation Link,
SCV001551334	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000252351

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Oct 1, 2013)

germline

clinical testing

Citation Link,

SCV001551334

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

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	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000252351.10

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

Description

p.Asn188Ser (AAT>AGT): c.563 A>G in exon 6 of the SURF1 gene (NM_003172.2) The c.563 A>G sequence change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. Multiple in-silico splice prediction models predict that c.563 A>G creates a cryptic donor site, which would be expected to lead to abnormal gene splicing. However, the true effect of c.563 A>G on splicing in vivo is not known. Therefore, based on the currently available information, it is unclear whether c.563 A>G is a disease-causing mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).

#	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 Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551334.1

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

Description

The SURF1 p.N188S variant was identified in dbSNP (ID: rs200702528) and ClinVar (classified as uncertain significance by Invitae and as likely pathogenic by GeneDx). The variant was identified in control databases in 31 of 281050 chromosomes at a frequency of 0.0001103 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.N188 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen- 2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. Functional analysis suggests that this variant does not affect protein expression, but has mild effects on complex IV assembly (Li_2018_PMID: 29933018). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome and Splice AI genome) do not predict an effect on splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.Â¬â€

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

Last Updated: Jun 23, 2024

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