NM_001348800.3(ZBTB20):c.1861C>T (p.Leu621Phe) AND Primrose syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 1, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000133613.4

Allele description [Variation Report for NM_001348800.3(ZBTB20):c.1861C>T (p.Leu621Phe)]

NM_001348800.3(ZBTB20):c.1861C>T (p.Leu621Phe)

Gene:

ZBTB20:zinc finger and BTB domain containing 20 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q13.31

Genomic location:

Preferred name:

NM_001348800.3(ZBTB20):c.1861C>T (p.Leu621Phe)

HGVS:

NC_000003.12:g.114339370G>A
NG_052992.1:g.812911C>T
NM_001164342.2:c.1861C>T
NM_001164343.2:c.1642C>T
NM_001164344.4:c.1642C>T
NM_001164345.4:c.1642C>T
NM_001164346.2:c.1642C>T
NM_001164347.2:c.1642C>T
NM_001348800.3:c.1861C>TMANE SELECT
NM_001348801.3:c.1642C>T
NM_001348802.3:c.1642C>T
NM_001348803.3:c.1861C>T
NM_001348804.3:c.1642C>T
NM_001348805.3:c.1642C>T
NM_001393393.1:c.1861C>T
NM_001393394.1:c.1861C>T
NM_001393395.1:c.1642C>T
NM_001393396.1:c.1642C>T
NM_015642.7:c.1642C>T
NP_001157814.1:p.Leu621Phe
NP_001157815.1:p.Leu548Phe
NP_001157816.1:p.Leu548Phe
NP_001157817.1:p.Leu548Phe
NP_001157818.1:p.Leu548Phe
NP_001157819.1:p.Leu548Phe
NP_001335729.1:p.Leu621Phe
NP_001335730.1:p.Leu548Phe
NP_001335731.1:p.Leu548Phe
NP_001335732.1:p.Leu621Phe
NP_001335733.1:p.Leu548Phe
NP_001335734.1:p.Leu548Phe
NP_001380322.1:p.Leu621Phe
NP_001380323.1:p.Leu621Phe
NP_001380324.1:p.Leu548Phe
NP_001380325.1:p.Leu548Phe
NP_056457.3:p.Leu548Phe
NC_000003.11:g.114058217G>A
NM_001164342.1:c.1861C>T
NR_121662.3:n.526C>T
Q9HC78:p.Leu621Phe

Protein change:

L548F; LEU621PHE

Links:

UniProtKB: Q9HC78#VAR_072586; OMIM: 606025.0002; dbSNP: rs483353070

NCBI 1000 Genomes Browser:

rs483353070

Molecular consequence:

NM_001164342.2:c.1861C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164343.2:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164344.4:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164345.4:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164346.2:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164347.2:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348800.3:c.1861C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348801.3:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348802.3:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348803.3:c.1861C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348804.3:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001348805.3:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001393393.1:c.1861C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001393394.1:c.1861C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001393395.1:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001393396.1:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015642.7:c.1642C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_121662.3:n.526C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Primrose syndrome
Synonyms:: Ossified ear cartilages with mental deficiency, muscle wasting, and bony changes; Intellectual disability-cataracts-calcified pinnae-myopathy syndrome
Identifiers:: MONDO: MONDO:0009798; MedGen: C0796121; OMIM: 259050

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000172006	Reparto di Fisiopatologia delle Malattie Genetiche, Dipartimento di Ematologia, Oncologia; Istituto Superiore di Sanità	no assertion criteria provided	pathogenic	de novo	not provided
SCV000188671	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2014)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 21567911, 25017102

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000172006

Reparto di Fisiopatologia delle Malattie Genetiche, Dipartimento di Ematologia, Oncologia; Istituto Superiore di Sanità

no assertion criteria provided

pathogenic

de novo

not provided

SCV000188671

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2014)

germline

literature only

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	de novo	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Additional features of unique Primrose syndrome phenotype.

Carvalho DR, Speck-Martins CE.

Am J Med Genet A. 2011 Jun;155A(6):1379-83. doi: 10.1002/ajmg.a.33955. Epub 2011 May 12.

PubMed [citation]

PMID:: 21567911

Mutations in ZBTB20 cause Primrose syndrome.

Cordeddu V, Redeker B, Stellacci E, Jongejan A, Fragale A, Bradley TE, Anselmi M, Ciolfi A, Cecchetti S, Muto V, Bernardini L, Azage M, Carvalho DR, Espay AJ, Male A, Molin AM, Posmyk R, Battisti C, Casertano A, Melis D, van Kampen A, Baas F, et al.

Nat Genet. 2014 Aug;46(8):815-7. doi: 10.1038/ng.3035. Epub 2014 Jul 13.

PubMed [citation]

PMID:: 25017102

Details of each submission

From Reparto di Fisiopatologia delle Malattie Genetiche, Dipartimento di Ematologia, Oncologia; Istituto Superiore di Sanità, SCV000172006.1

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

Description

Converted during submission to Pathogenic.

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

From OMIM, SCV000188671.2

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

Description

In a 26-year-old man with Primrose syndrome (PRIMS; 259050), originally reported by Carvalho and Speck-Martins (2011), Cordeddu et al. (2014) identified heterozygosity for a de novo c.1861C-T transition in exon 4 of the ZBTB20 gene, resulting in a leu621-to-phe (L621F) substitution at a highly conserved residue in the second zinc finger. Assays in transfected HEK293T cells demonstrated strongly reduced DNA binding for the L621F mutant, which correlated with strongly reduced ability to repress transcription of a reporter gene. Reduced levels of DNA-bound ZBTB20 and less efficient AFP promoter repression were also observed in cells coexpressing the wildtype protein and the L621F mutant, consistent with a dominant-negative effect of the mutant on the wildtype allele.

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

Last Updated: Apr 15, 2023

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