NM_001278431.2(C1QTNF5):c.562C>A (p.Pro188Thr) AND Late-onset retinal degeneration

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 27, 2022
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:: RCV002250440.1

Allele description [Variation Report for NM_001278431.2(C1QTNF5):c.562C>A (p.Pro188Thr)]

NM_001278431.2(C1QTNF5):c.562C>A (p.Pro188Thr)

Genes:

C1QTNF5:C1q and TNF related 5 [Gene - OMIM - HGNC]
MFRP:membrane frizzled-related protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_001278431.2(C1QTNF5):c.562C>A (p.Pro188Thr)

HGVS:

NC_000011.10:g.119339501G>T
NG_012235.1:g.12173C>A
NM_001278431.2:c.562C>AMANE SELECT
NM_015645.5:c.562C>A
NM_031433.4:c.*1458C>AMANE SELECT
NP_001265360.1:p.Pro188Thr
NP_056460.1:p.Pro188Thr
NC_000011.9:g.119210211G>T

Protein change:

P188T

Links:

dbSNP: rs1591299252

NCBI 1000 Genomes Browser:

rs1591299252

Molecular consequence:

NM_031433.4:c.*1458C>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001278431.2:c.562C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015645.5:c.562C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Late-onset retinal degeneration (LORD)
Synonyms:: RETINAL DEGENERATION, LATE-ONSET, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0011579; MedGen: C1854065; Orphanet: 67042; OMIM: 605670

Recent activity

Clear Turn Off Turn On

MATH domain-containing protein [Caenorhabditis elegans]
MATH domain-containing protein [Caenorhabditis elegans]
gi|17566082|ref|NP_507531.1|

Protein
Mus musculus transmembrane protein 38B (Tmem38b), mRNA
Mus musculus transmembrane protein 38B (Tmem38b), mRNA
gi|293335837|ref|NM_028053.2|

Nucleotide
Homo sapiens TTC28 antisense RNA 1 (TTC28-AS1), transcript variant 1, long non-c...
Homo sapiens TTC28 antisense RNA 1 (TTC28-AS1), transcript variant 1, long non-coding RNA
gi|224028240|ref|NR_026963.1|

Nucleotide
Homo sapiens coiled-coil domain containing 136 (CCDC136), transcript variant 5, ...
Homo sapiens coiled-coil domain containing 136 (CCDC136), transcript variant 5, mRNA
gi|1535530853|ref|NM_001367761.1|

Nucleotide
PREDICTED: Homo sapiens SID1 transmembrane family member 1 (SIDT1), transcript v...
PREDICTED: Homo sapiens SID1 transmembrane family member 1 (SIDT1), transcript variant X8, mRNA
gi|2217344568|ref|XM_047448381.1|

Nucleotide

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
SCV002520685	Institute of Human Genetics, University of Goettingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33949280, 28939808, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520685

Institute of Human Genetics, University of Goettingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 27, 2022)

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the C1QTNF5 gene.

De Zaeytijd J, Coppieters F, De Bruyne M, Van Royen J, Roels D, Six R, Van Cauwenbergh C, De Baere E, Leroy BP.

Ophthalmic Genet. 2021 Oct;42(5):521-532. doi: 10.1080/13816810.2021.1923041. Epub 2021 May 5.

PubMed [citation]

PMID:: 33949280

Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration.

Stanton CM, Borooah S, Drake C, Marsh JA, Campbell S, Lennon A, Soares DC, Vallabh NA, Sahni J, Cideciyan AV, Dhillon B, Vitart V, Jacobson SG, Wright AF, Hayward C.

Sci Rep. 2017 Sep 22;7(1):12147. doi: 10.1038/s41598-017-11898-3.

PubMed [citation]

PMID:: 28939808
PMCID:: PMC5610255

See all PubMed Citations (3)

Details of each submission

From Institute of Human Genetics, University of Goettingen, SCV002520685.1

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

Description

The variant c.562C>A (p.(Pro188Thr)) in exon 15 of the C1QTNF5-gene is not found in the gnomAD database, it affects a moderately conserved nucleotide, a highly conserved amino acid within a protein domain and there is a small physicochemical difference between Pro and Thr. This mutation has already been described to be pathogenic in the literature (PMID: 33949280) and functional studies have shown a deleterious effect of this variant on protein function (PMID: 28939808). Also, p.Pro188Thr is a missense mutation at an amino acid residue where another missense change determined to be pathogenic has been already described (p.Pro188Leu, PMID: 32036094). This variant has a pathogenic computational verdict based in silico prediction models. ACMG criteria used for classification: PS3, PM2, PM5, PP2, PP3, PP5.

#	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		1	not provided	not provided	not provided

Last Updated: Nov 10, 2024

ClinVar

Relating variation to medicine