rs119456963
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_153240.5(NPHP3):c.2918G>A(p.Arg973Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
NPHP3
NM_153240.5 missense
NM_153240.5 missense
Scores
9
4
6
Clinical Significance
Conservation
PhyloP100: 7.71
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.801
PP5
?
Variant 3-132688857-C-T is Pathogenic according to our data. Variant chr3-132688857-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2637.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHP3 | NM_153240.5 | c.2918G>A | p.Arg973Gln | missense_variant | 21/27 | ENST00000337331.10 | |
NPHP3-ACAD11 | NR_037804.1 | n.2924G>A | non_coding_transcript_exon_variant | 20/45 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHP3 | ENST00000337331.10 | c.2918G>A | p.Arg973Gln | missense_variant | 21/27 | 1 | NM_153240.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151946Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251054Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135680
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6AN XY: 727208
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Renal-hepatic-pancreatic dysplasia 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2008 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
A;A
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of glycosylation at T975 (P = 0.0348);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at