NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter) AND Autosomal recessive nonsyndromic hearing loss 70

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
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:: RCV002283958.1

Allele description [Variation Report for NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)]

NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)

Gene:

PNPT1:polyribonucleotide nucleotidyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.1

Genomic location:

Preferred name:

NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)

HGVS:

NC_000002.12:g.55679787G>A
NG_033012.1:g.19124C>T
NM_033109.5:c.574C>TMANE SELECT
NP_149100.2:p.Arg192Ter
NC_000002.11:g.55906922G>A
NM_033109.4:c.574C>T

Protein change:

R192*

Molecular consequence:

NM_033109.5:c.574C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 70
Synonyms:: Deafness, autosomal recessive 70
Identifiers:: MONDO: MONDO:0013978; MedGen: C1824925; Orphanet: 90636; OMIM: 614934

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002573219	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28594066, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002573219

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2022)

germline

clinical testing

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	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Novel biallelic mutations in the PNPT1 gene encoding a mitochondrial-RNA-import protein PNPase cause delayed myelination.

Sato R, Arai-Ichinoi N, Kikuchi A, Matsuhashi T, Numata-Uematsu Y, Uematsu M, Fujii Y, Murayama K, Ohtake A, Abe T, Kure S.

Clin Genet. 2018 Feb;93(2):242-247. doi: 10.1111/cge.13068. Epub 2017 Oct 4.

PubMed [citation]

PMID:: 28594066

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, SCV002573219.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 28594066). The variant has been reported to be associated with PNPT1-related disorder (PMID: 28594066). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Aug 5, 2023

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