3-132681258-CTT-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_153240.5(NPHP3):c.*650_*651del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 105,186 control chromosomes in the GnomAD database, including 200 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.089 ( 200 hom., cov: 23)
Exomes 𝑓: 0.027 ( 0 hom. )
Consequence
NPHP3
NM_153240.5 3_prime_UTR
NM_153240.5 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.19
Genes affected
NPHP3 (HGNC:7907): (nephrocystin 3) This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protein interacts with nephrocystin, it is required for normal ciliary development, and it functions in renal tubular development. Mutations in this gene are associated with nephronophthisis type 3, and also with renal-hepatic-pancreatic dysplasia, and Meckel syndrome type 7. Naturally occurring read-through transcripts exist between this gene and the downstream ACAD11 (acyl-CoA dehydrogenase family, member 11) gene. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPHP3 | NM_153240.5 | c.*650_*651del | 3_prime_UTR_variant | 27/27 | ENST00000337331.10 | NP_694972.3 | ||
NPHP3-ACAD11 | NR_037804.1 | n.3995+654_3995+655del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHP3 | ENST00000337331.10 | c.*650_*651del | 3_prime_UTR_variant | 27/27 | 1 | NM_153240.5 | ENSP00000338766 | P1 | ||
NPHP3 | ENST00000474871.5 | n.3842_3843del | non_coding_transcript_exon_variant | 11/11 | 2 | |||||
NPHP3 | ENST00000493732.5 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0890 AC: 9350AN: 105104Hom.: 200 Cov.: 23
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GnomAD4 exome AF: 0.0270 AC: 2AN: 74Hom.: 0 AF XY: 0.0370 AC XY: 2AN XY: 54
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GnomAD4 genome AF: 0.0889 AC: 9348AN: 105112Hom.: 200 Cov.: 23 AF XY: 0.0897 AC XY: 4386AN XY: 48914
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Renal-hepatic-pancreatic dysplasia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Meckel-Gruber syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 14, 2021 | - - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at