chr2-110123866-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001128178.3(NPHP1):c.1959C>T(p.Asp653=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,950 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
NPHP1
NM_001128178.3 synonymous
NM_001128178.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.58
Genes affected
NPHP1 (HGNC:7905): (nephrocystin 1) This gene encodes a protein with src homology domain 3 (SH3) patterns. This protein interacts with Crk-associated substrate, and it appears to function in the control of cell division, as well as in cell-cell and cell-matrix adhesion signaling, likely as part of a multifunctional complex localized in actin- and microtubule-based structures. Mutations in this gene cause familial juvenile nephronophthisis type 1, a kidney disorder involving both tubules and glomeruli. Defects in this gene are also associated with Senior-Loken syndrome type 1, also referred to as juvenile nephronophthisis with Leber amaurosis, which is characterized by kidney and eye disease, and with Joubert syndrome type 4, which is characterized by cerebellar ataxia, oculomotor apraxia, psychomotor delay and neonatal breathing abnormalities, sometimes including retinal dystrophy and renal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 2-110123866-G-A is Benign according to our data. Variant chr2-110123866-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1116415.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.58 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP1 | NM_001128178.3 | c.1959C>T | p.Asp653= | synonymous_variant | 20/20 | ENST00000445609.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP1 | ENST00000445609.7 | c.1959C>T | p.Asp653= | synonymous_variant | 20/20 | 1 | NM_001128178.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251484Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135914
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GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727210
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74336
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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 09, 2023 | - - |
Computational scores
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Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at