NM_207037.2(TCF12):c.1541C>A (p.Ser514Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 1, 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:: RCV003660868.2

Allele description [Variation Report for NM_207037.2(TCF12):c.1541C>A (p.Ser514Ter)]

NM_207037.2(TCF12):c.1541C>A (p.Ser514Ter)

Gene:

TCF12:transcription factor 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q21.3

Genomic location:

Preferred name:

NM_207037.2(TCF12):c.1541C>A (p.Ser514Ter)

HGVS:

NC_000015.10:g.57262167C>A
NG_033851.2:g.349078C>A
NM_001306219.3:c.1031C>A
NM_001306220.3:c.761C>A
NM_001322151.2:c.1541C>A
NM_001322152.2:c.1541C>A
NM_001322154.2:c.884C>A
NM_001322156.2:c.1367C>A
NM_001322157.3:c.1469C>A
NM_001322158.2:c.1295C>A
NM_001322159.3:c.1541C>A
NM_001322161.2:c.1538C>A
NM_001322162.2:c.1541C>A
NM_001322164.2:c.1505C>A
NM_001322165.2:c.1469C>A
NM_003205.4:c.1469C>A
NM_207036.2:c.1541C>A
NM_207037.2:c.1541C>AMANE SELECT
NM_207038.2:c.1469C>A
NM_207040.2:c.959C>A
NP_001293148.1:p.Ser344Ter
NP_001293149.1:p.Ser254Ter
NP_001309080.1:p.Ser514Ter
NP_001309081.1:p.Ser514Ter
NP_001309083.1:p.Ser295Ter
NP_001309085.1:p.Ser456Ter
NP_001309086.1:p.Ser490Ter
NP_001309087.1:p.Ser432Ter
NP_001309088.1:p.Ser514Ter
NP_001309090.1:p.Ser513Ter
NP_001309091.1:p.Ser514Ter
NP_001309093.1:p.Ser502Ter
NP_001309094.1:p.Ser490Ter
NP_003196.1:p.Ser490Ter
NP_996919.1:p.Ser514Ter
NP_996920.1:p.Ser514Ter
NP_996921.1:p.Ser490Ter
NP_996923.1:p.Ser320Ter
NC_000015.9:g.57554365C>A
NC_000015.9:g.57554365C>A
NM_207036.1:c.1541C>A

Protein change:

S254*

Links:

dbSNP: rs2060619071

NCBI 1000 Genomes Browser:

rs2060619071

Molecular consequence:

NM_001306219.3:c.1031C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001306220.3:c.761C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322151.2:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322152.2:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322154.2:c.884C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322156.2:c.1367C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322157.3:c.1469C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322158.2:c.1295C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322159.3:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322161.2:c.1538C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322162.2:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322164.2:c.1505C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322165.2:c.1469C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_003205.4:c.1469C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_207036.2:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_207037.2:c.1541C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_207038.2:c.1469C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_207040.2:c.959C>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004375328	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23354436, 32620954, 33547006, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004375328

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 1, 2023)

germline

clinical testing

PubMed (4)
[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

Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.

Sharma VP, Fenwick AL, Brockop MS, McGowan SJ, Goos JA, Hoogeboom AJ, Brady AF, Jeelani NO, Lynch SA, Mulliken JB, Murray DJ, Phipps JM, Sweeney E, Tomkins SE, Wilson LC, Bennett S, Cornall RJ, Broxholme J, Kanapin A; 500 Whole-Genome Sequences (WGS500) Consortium., Johnson D, Wall SA, et al.

Nat Genet. 2013 Mar;45(3):304-7. doi: 10.1038/ng.2531. Epub 2013 Jan 27. Erratum in: Nat Genet. 2013 Oct;45(10):1261.

PubMed [citation]

PMID:: 23354436
PMCID:: PMC3647333

TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.

Davis EE, Balasubramanian R, Kupchinsky ZA, Keefe DL, Plummer L, Khan K, Meczekalski B, Heath KE, Lopez-Gonzalez V, Ballesta-Martinez MJ, Margabanthu G, Price S, Greening J, Brauner R, Valenzuela I, Cusco I, Fernandez-Alvarez P, Wierman ME, Li T, Lage K, Barroso PS, Chan YM, et al.

Hum Mol Genet. 2020 Aug 11;29(14):2435-2450. doi: 10.1093/hmg/ddaa120.

PubMed [citation]

PMID:: 32620954
PMCID:: PMC7608740

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004375328.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ser514*) in the TCF12 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCF12 are known to be pathogenic (PMID: 23354436, 32620954). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with craniosynostosis (PMID: 33547006). ClinVar contains an entry for this variant (Variation ID: 930393). For these reasons, this variant has been classified as Pathogenic.

#	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 29, 2024

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