NM_021619.3(PRDM12):c.516G>C (p.Glu172Asp) AND Congenital insensitivity to pain-hypohidrosis syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 21, 2016
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:: RCV000239564.2

Allele description [Variation Report for NM_021619.3(PRDM12):c.516G>C (p.Glu172Asp)]

NM_021619.3(PRDM12):c.516G>C (p.Glu172Asp)

Gene:

PRDM12:PR/SET domain 12 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.12

Genomic location:

Preferred name:

NM_021619.3(PRDM12):c.516G>C (p.Glu172Asp)

HGVS:

NC_000009.12:g.130668259G>C
NG_053081.1:g.8666G>C
NM_021619.3:c.516G>CMANE SELECT
NP_067632.2:p.Glu172Asp
NC_000009.11:g.133543646G>C
NM_021619.2:c.516G>C
Q9H4Q4:p.Glu172Asp

Protein change:

E172D; GLU172ASP

Links:

UniProtKB: Q9H4Q4#VAR_074621; OMIM: 616458.0004; dbSNP: rs755205487

NCBI 1000 Genomes Browser:

rs755205487

Molecular consequence:

NM_021619.3:c.516G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Congenital insensitivity to pain-hypohidrosis syndrome
Synonyms:: HSAN VIII; Neuropathy, hereditary sensory and autonomic, type VIII
Identifiers:: MONDO: MONDO:0014662; MedGen: C4225308; OMIM: 616488

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000297919	OMIM	no assertion criteria provided	Pathogenic (Aug 10, 2016)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 26005867, 25891934
SCV001429152	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 21, 2016)	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

SCV000297919

OMIM

no assertion criteria provided

Pathogenic
(Aug 10, 2016)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001429152

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 21, 2016)

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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Transcriptional regulator PRDM12 is essential for human pain perception.

Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous AC, Strom TM, Samara C, Moore AW, Cho LT, Young GT, Weiss C, Schabhüttl M, Stucka R, Schmid AB, Parman Y, Graul-Neumann L, Heinritz W, Passarge E, Watson RM, Hertz JM, Moog U, Baumgartner M, et al.

Nat Genet. 2015 Jul;47(7):803-8. doi: 10.1038/ng.3308. Epub 2015 May 25. Erratum in: Nat Genet. 2015 Aug;47(8):962.

PubMed [citation]

PMID:: 26005867
PMCID:: PMC7212047

The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception.

Nagy V, Cole T, Van Campenhout C, Khoung TM, Leung C, Vermeiren S, Novatchkova M, Wenzel D, Cikes D, Polyansky AA, Kozieradzki I, Meixner A, Bellefroid EJ, Neely GG, Penninger JM.

Cell Cycle. 2015;14(12):1799-808. doi: 10.1080/15384101.2015.1036209. Erratum in: Cell Cycle. 2015;14(19):3203.

PubMed [citation]

PMID:: 25891934
PMCID:: PMC4613559

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000297919.1

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

Description

In a Turkish patient (family D), born of consanguineous parents, with hereditary sensory and autonomic neuropathy type VIII (HSAN8; 616488), Chen et al. (2015) identified a homozygous c.516G-C transversion (c.516G-C, NM_021619.2) in the PRDM12 gene, resulting in a glu172-to-asp (E172D) substitution at a highly conserved residue in the PR/SET domain. The mutation, which was found by exome sequencing, segregated with the disorder in the family and was not found in the dbSNP (build 138), 1000 Genomes Project, or Exome Variant Server databases, or in an in-house control database. In vitro functional expression studies showed that the mutant protein was expressed normally but had lost the ability to induce dimethylation on H3K9 in Xenopus neurula.

Nagy et al. (2015) demonstrated that the E172D mutant protein clustered into large aggregates in the nucleus of HEK293 cells.

#	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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001429152.1

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

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

Last Updated: Apr 23, 2022

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