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GeneBe

rs146890274

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153240.5(NPHP3):c.3281G>T(p.Arg1094Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1094Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NPHP3
NM_153240.5 missense

Scores

3
11
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.50
Variant links:
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPHP3NM_153240.5 linkuse as main transcriptc.3281G>T p.Arg1094Leu missense_variant 23/27 ENST00000337331.10
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.3287G>T non_coding_transcript_exon_variant 22/45

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPHP3ENST00000337331.10 linkuse as main transcriptc.3281G>T p.Arg1094Leu missense_variant 23/271 NM_153240.5 P1Q7Z494-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
Cadd
Pathogenic
27
Dann
Uncertain
1.0
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.28
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Benign
0.80
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.63
Sift
Benign
0.13
T
Sift4G
Uncertain
0.024
D
Polyphen
0.93
P
Vest4
0.72
MutPred
0.48
Gain of glycosylation at T1089 (P = 0.0225);
MVP
0.94
MPC
0.79
ClinPred
0.81
D
GERP RS
5.7
Varity_R
0.22
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.38
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.38
Position offset: -48

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs146890274; hg19: chr3-132405152; API