ClinVar Miner

Submissions for variant NM_001128178.3(NPHP1):c.771+2C>T

gnomAD frequency: 0.00022  dbSNP: rs189320299
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000078491 SCV000110347 uncertain significance not provided 2017-12-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001243180 SCV001416319 uncertain significance Nephronophthisis 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 258 of the NPHP1 protein (p.Ala258Val). This variant is present in population databases (rs189320299, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with NPHP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 92720). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002483130 SCV002794111 uncertain significance Joubert syndrome with renal defect; Nephronophthisis 1; Senior-Loken syndrome 1 2021-07-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002514380 SCV003702832 uncertain significance Inborn genetic diseases 2022-08-18 criteria provided, single submitter clinical testing The c.773C>T (p.A258V) alteration is located in exon 8 (coding exon 8) of the NPHP1 gene. This alteration results from a C to T substitution at nucleotide position 773, causing the alanine (A) at amino acid position 258 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV000078491 SCV003805541 likely benign not provided 2021-05-26 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
PreventionGenetics, part of Exact Sciences RCV004734635 SCV005362227 uncertain significance NPHP1-related disorder 2024-08-09 no assertion criteria provided clinical testing The NPHP1 c.771+2C>T variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD. On an alternative transcript (NM_001128178.1), this variant is designated c.771+2C>T, and is predicted to interfere with splicing (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). However, the use of computer prediction programs is not equivalent to functional evidence, and therefore the clinical significance of this variant is uncertain.

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