NM_153240.5(NPHP3):c.2694-2_2694-1del AND Nephronophthisis

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 24, 2026
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000205615.17

Allele description [Variation Report for NM_153240.5(NPHP3):c.2694-2_2694-1del]

NM_153240.5(NPHP3):c.2694-2_2694-1del

Genes:

NPHP3-ACAD11:NPHP3-ACAD11 readthrough (NMD candidate) [Gene - HGNC]
NPHP3:nephrocystin 3 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_153240.5(NPHP3):c.2694-2_2694-1del

Other names:

splice site

HGVS:

NC_000003.12:g.132689264_132689265del
NG_008130.2:g.38168_38169del
NM_153240.5:c.2694-2_2694-1delMANE SELECT
NC_000003.11:g.132408108_132408109del
NG_008130.1:g.38168_38169del
NM_153240.4:c.2694-2_2694-1del
NM_153240.4:c.2694-2_2694-1delAG
NM_153240.5:c.2694-2_2694-1delAGMANE SELECT
c.2694-2_2694-1delAG

Links:

OMIM: 608002.0004; dbSNP: rs751527253

Molecular consequence:

NM_153240.5:c.2694-2_2694-1del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000261757	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 24, 2026)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18371931, 23559409, 26673778, 20007846, 28492532
SCV007095766	Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 7, 2025)	maternal	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

SCV000261757

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 24, 2026)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV007095766

Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 7, 2025)

maternal

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Loss of nephrocystin-3 function can cause embryonic lethality, Meckel-Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic dysplasia.

Bergmann C, Fliegauf M, Brüchle NO, Frank V, Olbrich H, Kirschner J, Schermer B, Schmedding I, Kispert A, Kränzlin B, Nürnberg G, Becker C, Grimm T, Girschick G, Lynch SA, Kelehan P, Senderek J, Neuhaus TJ, Stallmach T, Zentgraf H, Nürnberg P, Gretz N, et al.

Am J Hum Genet. 2008 Apr;82(4):959-70. doi: 10.1016/j.ajhg.2008.02.017. Epub 2008 Mar 27.

PubMed [citation]

PMID:: 18371931
PMCID:: PMC2427297

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

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000261757.13

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a splice site in intron 19 of the NPHP3 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs751527253, gnomAD 0.05%). Disruption of this splice site has been observed in individual(s) with Meckel-Gruber-like syndrome and/or nephronophthisis-related ciliopathy (PMID: 18371931, 20007846, 23559409, 26673778). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220868). Studies have shown that disruption of this splice site results in activation of a cryptic splice site, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 20007846). For these reasons, this variant has been classified as Pathogenic.

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

From Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals, SCV007095766.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 14, 2026

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