NM_001367624.2(ZNF469):c.3321G>A (p.Arg1107=) AND Brittle cornea syndrome 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 17, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000266288.7

Allele description [Variation Report for NM_001367624.2(ZNF469):c.3321G>A (p.Arg1107=)]

NM_001367624.2(ZNF469):c.3321G>A (p.Arg1107=)

Gene:

ZNF469:zinc finger protein 469 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q24.2

Genomic location:

Preferred name:

NM_001367624.2(ZNF469):c.3321G>A (p.Arg1107=)

Other names:

NM_001127464.1:c.3237G>A; NM_001127464.2:c.3237G>A

HGVS:

NC_000016.10:g.88430791G>A
NG_012236.2:g.8321G>A
NM_001367624.2:c.3321G>AMANE SELECT
NP_001354553.1:p.Arg1107=
NC_000016.9:g.88497199G>A

Links:

dbSNP: rs763826959

NCBI 1000 Genomes Browser:

rs763826959

Molecular consequence:

NM_001367624.2:c.3321G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:: Brittle cornea syndrome 1 (BCS1)
Synonyms:: EDS6B; EDS VIB (formerly); Ehlers-Danlos syndrome type 6B (formerly); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0024543; MedGen: C0268344; Orphanet: 90354; OMIM: 229200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000399319	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Uncertain significance (Jun 14, 2016)	germline	clinical testing	ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV003920640	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000399319

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification 20161018)

Uncertain significance
(Jun 14, 2016)

germline

clinical testing

ICSL_Variant_Classification_20161018.pdf,

Citation Link,

SCV003920640

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jan 17, 2023)

germline

clinical testing

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

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

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 Illumina Laboratory Services, Illumina, SCV000399319.2

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

#	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

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920640.1

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

Description

This variant has not been reported in thel literature. It is present in gnomAD (Highest reported MAF: 0.007% [47/67984]; https://gnomad.broadinstitute.org/variant/16-88430791-G-A?dataset=gnomad_r3), and in ClinVar, with classifications ranging from likely benign to uncertain significance (Variation ID: 320905). Of note, this is a silent variant and thus does not change the amino acid, it occurs at a nucleotide position that is poorly conserved evolutionarily, and it is not predicted to impact splicing; this reduces the probability that this variant is disease-causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.

#	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: May 1, 2024

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