3-132722002-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_153240.5(NPHP3):c.354G>A(p.Lys118Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,902 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: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
NPHP3
NM_153240.5 synonymous
NM_153240.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.847
Publications
0 publications found
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)
NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 3-132722002-C-T is Benign according to our data. Variant chr3-132722002-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 531635.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.847 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_153240.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NPHP3 | NM_153240.5 | MANE Select | c.354G>A | p.Lys118Lys | synonymous | Exon 1 of 27 | NP_694972.3 | ||
| NPHP3-AS1 | NR_002811.2 | n.253C>T | non_coding_transcript_exon | Exon 1 of 11 | |||||
| NPHP3-ACAD11 | NR_037804.1 | n.458G>A | non_coding_transcript_exon | Exon 1 of 45 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| NPHP3 | ENST00000337331.10 | TSL:1 MANE Select | c.354G>A | p.Lys118Lys | synonymous | Exon 1 of 27 | ENSP00000338766.5 | ||
| NPHP3 | ENST00000383282.3 | TSL:1 | c.354G>A | p.Lys118Lys | synonymous | Exon 1 of 2 | ENSP00000372769.2 | ||
| NPHP3-AS1 | ENST00000489343.5 | TSL:1 | n.253C>T | non_coding_transcript_exon | Exon 1 of 5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.0000121 AC: 3AN: 248238 AF XY: 0.00000739 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
248238
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460902Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726792 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1460902
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
726792
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33474
American (AMR)
AF:
AC:
3
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26122
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
52594
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111896
Other (OTH)
AF:
AC:
1
AN:
60378
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.538
Heterozygous variant carriers
0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis Benign:1
Oct 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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