U.S. flag

An official website of the United States government

NM_003143.3(SSBP1):c.119G>T (p.Gly40Val) AND Optic atrophy 13 with retinal and foveal abnormalities

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Apr 20, 2023
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:
RCV001255187.3

Allele description [Variation Report for NM_003143.3(SSBP1):c.119G>T (p.Gly40Val)]

NM_003143.3(SSBP1):c.119G>T (p.Gly40Val)

Gene:
SSBP1:single stranded DNA binding protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q34
Genomic location:
Preferred name:
NM_003143.3(SSBP1):c.119G>T (p.Gly40Val)
HGVS:
  • NC_000007.14:g.141743594G>T
  • NM_001256510.1:c.119G>T
  • NM_001256511.1:c.119G>T
  • NM_001256512.1:c.119G>T
  • NM_001256513.1:c.119G>T
  • NM_003143.3:c.119G>TMANE SELECT
  • NP_001243439.1:p.Gly40Val
  • NP_001243440.1:p.Gly40Val
  • NP_001243441.1:p.Gly40Val
  • NP_001243442.1:p.Gly40Val
  • NP_003134.1:p.Gly40Val
  • NC_000007.13:g.141443394G>T
  • NM_003143.2:c.119G>T
  • NR_046269.1:n.302G>T
Protein change:
G40V; GLY40VAL
Links:
OMIM: 600439.0004; dbSNP: rs1799653139
NCBI 1000 Genomes Browser:
rs1799653139
Molecular consequence:
  • NM_001256510.1:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256511.1:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256512.1:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001256513.1:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003143.3:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_046269.1:n.302G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Optic atrophy 13 with retinal and foveal abnormalities
Synonyms:
Optic atrophy with negative electroretinograms
Identifiers:
MONDO: MONDO:0008135; MedGen: C5435585; OMIM: 165510

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001431541OMIM
no assertion criteria provided
Pathogenic
(Sep 3, 2020) 		germlineliterature only

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

SCV003919059Duke University Health System Sequencing Clinic, Duke University Health System
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Apr 20, 2023) 		de novoresearch

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedde novoyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.

Del Dotto V, Ullah F, Di Meo I, Magini P, Gusic M, Maresca A, Caporali L, Palombo F, Tagliavini F, Baugh EH, Macao B, Szilagyi Z, Peron C, Gustafson MA, Khan K, La Morgia C, Barboni P, Carbonelli M, Valentino ML, Liguori R, Shashi V, Sullivan J, et al.

J Clin Invest. 2020 Jan 2;130(1):108-125. doi: 10.1172/JCI128514.

PubMed [citation]
PMID:
31550240
PMCID:
PMC6934201

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 OMIM, SCV001431541.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a woman (patient 3), born of unrelated parents (family 2), with optic atrophy-13 with retinal and foveal abnormalities (OPA13; 165510), Del Dotto et al. (2020) identified a de novo heterozygous c.119G-T transversion (c.119G-T, NM_003143.2) in the SSBP1 gene, resulting in a gly40-to-val (G40V) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Western blot analysis of patient fibroblasts showed that the G40V mutant had increased protein levels compared to controls. In vitro studies of patient fibroblasts showed mtDNA depletion, decreased ability to stimulate POLG1-induced DNA synthesis, and a partial defect in mitochondrial oxidative respiration. Expression of the G40V mutation into ssbp1-null zebrafish failed to rescue the abnormal optic nerve phenotype, suggesting that the mutation causes a loss of function.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Duke University Health System Sequencing Clinic, Duke University Health System, SCV003919059.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2023