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NM_007055.4(POLR3A):c.3337-11T>C AND Leukoencephalopathy, ataxia, hypodontia, hypomyelination syndrome

Germline classification:
Pathogenic (1 submission)
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:
RCV003313969.8

Allele description

NM_007055.4(POLR3A):c.3337-11T>C

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.3337-11T>C
HGVS:
  • NC_000010.11:g.77984023A>G
  • NG_029648.1:g.50518T>C
  • NM_007055.4:c.3337-11T>CMANE SELECT
  • NC_000010.10:g.79743781A>G
  • NM_007055.3:c.3337-11T>C
Links:
OMIM: 614258.0010; dbSNP: rs1564613755
NCBI 1000 Genomes Browser:
rs1564613755
Molecular consequence:
  • NM_007055.4:c.3337-11T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Leukoencephalopathy, ataxia, hypodontia, hypomyelination syndrome (HLD7)
Synonyms:
LEUKODYSTROPHY, HYPOMYELINATING, 7, WITH OR WITHOUT OLIGODONTIA AND/OR HYPOGONADOTROPIC HYPOGONADISM; LEUKOENCEPHALOPATHY, HYPOMYELINATING, WITH ATAXIA AND DELAYED DENTITION; ATAXIA, DELAYED DENTITION, AND HYPOMYELINATION; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011897; MedGen: C4706676; Orphanet: 137639; Orphanet: 447893; Orphanet: 447896; Orphanet: 77295; Orphanet: 88637; OMIM: 607694

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0040138173billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenicunknownclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Bi-allelic POLR3A Loss-of-Function Variants Cause Autosomal-Recessive Wiedemann-Rautenstrauch Syndrome.

Wambach JA, Wegner DJ, Patni N, Kircher M, Willing MC, Baldridge D, Xing C, Agarwal AK, Vergano SAS, Patel C, Grange DK, Kenney A, Najaf T, Nickerson DA, Bamshad MJ, Cole FS, Garg A.

Am J Hum Genet. 2018 Dec 6;103(6):968-975. doi: 10.1016/j.ajhg.2018.10.010. Epub 2018 Nov 7.

PubMed [citation]
PMID:
30414627
PMCID:
PMC6288318

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 3billion, SCV004013817.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Intronic variant. In silico tools do not predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.05). However, it is reported to alter splicing, resulting in an in-frame exon 26 deletion (PMID: 30414627) The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least 2 similarly affected unrelated individuals (PMID: 30414627). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000549559). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Feb 16, 2025