rs773521620
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_153240.5(NPHP3):c.60C>T(p.Tyr20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000886 in 1,579,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000091 ( 0 hom. )
Consequence
NPHP3
NM_153240.5 synonymous
NM_153240.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.229
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]
NPHP3-AS1 (HGNC:24129): (NPHP3 antisense RNA 1)
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 3-132722296-G-A is Benign according to our data. Variant chr3-132722296-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2996949.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.229 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP3 | NM_153240.5 | c.60C>T | p.Tyr20= | synonymous_variant | 1/27 | ENST00000337331.10 | |
NPHP3-AS1 | NR_002811.2 | n.547G>A | non_coding_transcript_exon_variant | 1/11 | |||
NPHP3-ACAD11 | NR_037804.1 | n.164C>T | non_coding_transcript_exon_variant | 1/45 | |||
NPHP3-AS1 | NR_152743.1 | n.547G>A | non_coding_transcript_exon_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP3 | ENST00000337331.10 | c.60C>T | p.Tyr20= | synonymous_variant | 1/27 | 1 | NM_153240.5 | P1 | |
NPHP3-AS1 | ENST00000504440.1 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151872Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000911 AC: 13AN: 1427772Hom.: 0 Cov.: 31 AF XY: 0.00000703 AC XY: 5AN XY: 710738
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at