NM_000362.5(TIMP3):c.484G>A (p.Glu162Lys) AND not provided

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 20, 2021
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:: RCV002043283.3

Allele description

NM_000362.5(TIMP3):c.484G>A (p.Glu162Lys)

Genes:

TIMP3:TIMP metallopeptidase inhibitor 3 [Gene - OMIM - HGNC]
SYN3:synapsin III [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.3

Genomic location:

Preferred name:

NM_000362.5(TIMP3):c.484G>A (p.Glu162Lys)

HGVS:

NC_000022.11:g.32859225G>A
NG_009117.2:g.62521G>A
NG_029545.1:g.204166C>T
NG_029545.2:g.204156C>T
NM_000362.5:c.484G>AMANE SELECT
NM_001135774.2:c.708+5690C>T
NM_001369907.1:c.711+5690C>T
NM_001369908.1:c.711+5690C>T
NM_001369909.1:c.708+5690C>T
NM_001369910.1:c.708+5690C>T
NM_003490.4:c.711+5690C>TMANE SELECT
NM_133633.3:c.711+5690C>T
NP_000353.1:p.Glu162Lys
NC_000022.10:g.33255212G>A

Protein change:

E162K

Links:

dbSNP: rs137853302

NCBI 1000 Genomes Browser:

rs137853302

Molecular consequence:

NM_001135774.2:c.708+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369907.1:c.711+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369908.1:c.711+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369909.1:c.708+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001369910.1:c.708+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_003490.4:c.711+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133633.3:c.711+5690C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000362.5:c.484G>A - 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
SCV002298790	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 20, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19536307, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002298790

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 20, 2021)

germline

clinical testing

PubMed (2)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and biochemical effects of the E139K missense mutation in the TIMP3 gene, associated with Sorsby fundus dystrophy.

Saihan Z, Li Z, Rice J, Rana NA, Ramsden S, Schlottmann PG, Jenkins SA, Blyth C, Black GC, McKie N, Webster AR.

Mol Vis. 2009 Jun 15;15:1218-30.

PubMed [citation]

PMID:: 19536307
PMCID:: PMC2697491

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002298790.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is also known as c.415G>A (p.E139K). This missense change has been observed in individual(s) with Sorsby fundus dystrophy (PMID: 19536307). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 162 of the TIMP3 protein (p.Glu162Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on TIMP3 function (PMID: 19536307).

#	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 16, 2024

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