U.S. flag

An official website of the United States government

NM_001128178.3(NPHP1):c.1886G>A (p.Trp629Ter) AND Nephronophthisis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 8, 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:
RCV001059818.8

Allele description [Variation Report for NM_001128178.3(NPHP1):c.1886G>A (p.Trp629Ter)]

NM_001128178.3(NPHP1):c.1886G>A (p.Trp629Ter)

Gene:
NPHP1:nephrocystin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q13
Genomic location:
Preferred name:
NM_001128178.3(NPHP1):c.1886G>A (p.Trp629Ter)
HGVS:
  • NC_000002.12:g.110123939C>T
  • NG_008287.1:g.86124G>A
  • NM_000272.5:c.2054G>A
  • NM_001128178.3:c.1886G>AMANE SELECT
  • NM_001128179.3:c.1697G>A
  • NM_001374256.1:c.1883G>A
  • NM_001374257.1:c.*128G>A
  • NM_207181.4:c.2051G>A
  • NP_000263.2:p.Trp685Ter
  • NP_001121650.1:p.Trp629Ter
  • NP_001121651.1:p.Trp566Ter
  • NP_001361185.1:p.Trp628Ter
  • NP_997064.2:p.Trp684Ter
  • NC_000002.11:g.110881516C>T
  • NM_000272.3:c.2054G>A
  • NM_000272.4:c.2054G>A
Protein change:
W566*
Links:
dbSNP: rs1311042980
NCBI 1000 Genomes Browser:
rs1311042980
Molecular consequence:
  • NM_001374257.1:c.*128G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000272.5:c.2054G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128178.3:c.1886G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128179.3:c.1697G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374256.1:c.1883G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_207181.4:c.2051G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Nephronophthisis
Synonyms:
juvenile nephronophthisis
Identifiers:
MONDO: MONDO:0019005; MedGen: C0687120; OMIM: PS256100; Human Phenotype Ontology: HP:0000090

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001224466Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 8, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy.

Halbritter J, Porath JD, Diaz KA, Braun DA, Kohl S, Chaki M, Allen SJ, Soliman NA, Hildebrandt F, Otto EA; GPN Study Group.

Hum Genet. 2013 Aug;132(8):865-84. doi: 10.1007/s00439-013-1297-0. Epub 2013 Apr 5.

PubMed [citation]
PMID:
23559409
PMCID:
PMC4643834

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224466.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the NPHP1 protein in which other variant(s) (p.Ser718*) have been determined to be pathogenic (PMID: 23559409). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 854715). This premature translational stop signal has been observed in individual(s) with clinical features of NPHP1-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp685*) in the NPHP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 49 amino acid(s) of the NPHP1 protein.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024