NM_007055.4(POLR3A):c.760C>T (p.Arg254Ter) AND Neonatal pseudo-hydrocephalic progeroid syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 1, 2018
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:: RCV000755671.6

Allele description [Variation Report for NM_007055.4(POLR3A):c.760C>T (p.Arg254Ter)]

NM_007055.4(POLR3A):c.760C>T (p.Arg254Ter)

Gene:

POLR3A:RNA polymerase III subunit A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.3

Genomic location:

Preferred name:

NM_007055.4(POLR3A):c.760C>T (p.Arg254Ter)

Other names:

NM_007055.4(POLR3A):c.760C>T; p.Arg254Ter

HGVS:

NC_000010.11:g.78022270G>A
NG_029648.1:g.12271C>T
NM_007055.4:c.760C>TMANE SELECT
NP_008986.2:p.Arg254Ter
NC_000010.10:g.79782028G>A
NM_007055.3:c.760C>T

Protein change:

R254*; ARG254TER

Links:

OMIM: 614258.0020; dbSNP: rs141659018

NCBI 1000 Genomes Browser:

rs141659018

Molecular consequence:

NM_007055.4:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Neonatal pseudo-hydrocephalic progeroid syndrome
Synonyms:: Wiedemann-Rautenstrauch syndrome
Identifiers:: MONDO: MONDO:0009910; MedGen: C0406586; Orphanet: 3455; OMIM: 264090

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000883073	OMIM	no assertion criteria provided	Pathogenic (Apr 2, 2024)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000886476	Cole/Wambach Lab, Washington University in St. Louis	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 1, 2018)	inherited	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 30414627
SCV001479499	University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Likely pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000883073

OMIM

no assertion criteria provided

Pathogenic
(Apr 2, 2024)

germline

literature only

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

SCV000886476

Cole/Wambach Lab, Washington University in St. Louis

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 1, 2018)

inherited

research

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

SCV001479499

University of Washington Center for Mendelian Genomics, University of Washington

no assertion criteria provided

Likely pathogenic

inherited

research

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

Analyses of LMNA-negative juvenile progeroid cases confirms biallelic POLR3A mutations in Wiedemann-Rautenstrauch-like syndrome and expands the phenotypic spectrum of PYCR1 mutations.

Lessel D, Ozel AB, Campbell SE, Saadi A, Arlt MF, McSweeney KM, Plaiasu V, Szakszon K, Szőllős A, Rusu C, Rojas AJ, Lopez-Valdez J, Thiele H, Nürnberg P, Nickerson DA, Bamshad MJ, Li JZ, Kubisch C, Glover TW, Gordon LB.

Hum Genet. 2018 Dec;137(11-12):921-939. doi: 10.1007/s00439-018-1957-1. Epub 2018 Nov 19.

PubMed [citation]

PMID:: 30450527
PMCID:: PMC6652186

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

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000883073.3

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

Description

For discussion of the c.760C-T transition in the POLR3A gene, resulting in an arg254-to-ter (R254X) substitution, that was found in compound heterozygosity in a 12.75-year-old girl (patient 4) with Wiedemann-Rautenstrauch syndrome (WDRTS; 264090) by Lessel et al. (2018), see 614258.0018.

#	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 Cole/Wambach Lab, Washington University in St. Louis, SCV000886476.1

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

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

From University of Washington Center for Mendelian Genomics, University of Washington, SCV001479499.1

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

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

Last Updated: Oct 20, 2024

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