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rs12631786

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153240.5(NPHP3):c.394-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,359,224 control chromosomes in the GnomAD database, including 26,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3561 hom., cov: 31)
Exomes 𝑓: 0.18 ( 23209 hom. )

Consequence

NPHP3
NM_153240.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0210
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 3-132719875-T-C is Benign according to our data. Variant chr3-132719875-T-C is described in ClinVar as [Benign]. Clinvar id is 262713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPHP3NM_153240.5 linkuse as main transcriptc.394-45A>G intron_variant ENST00000337331.10
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.498-45A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPHP3ENST00000337331.10 linkuse as main transcriptc.394-45A>G intron_variant 1 NM_153240.5 P1Q7Z494-1

Frequencies

GnomAD3 genomes
AF:
0.205
AC:
30681
AN:
149458
Hom.:
3564
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.221
Gnomad AMI
AF:
0.335
Gnomad AMR
AF:
0.184
Gnomad ASJ
AF:
0.144
Gnomad EAS
AF:
0.558
Gnomad SAS
AF:
0.283
Gnomad FIN
AF:
0.214
Gnomad MID
AF:
0.264
Gnomad NFE
AF:
0.168
Gnomad OTH
AF:
0.205
GnomAD3 exomes
AF:
0.227
AC:
41723
AN:
183714
Hom.:
5570
AF XY:
0.227
AC XY:
22606
AN XY:
99510
show subpopulations
Gnomad AFR exome
AF:
0.231
Gnomad AMR exome
AF:
0.177
Gnomad ASJ exome
AF:
0.167
Gnomad EAS exome
AF:
0.568
Gnomad SAS exome
AF:
0.267
Gnomad FIN exome
AF:
0.220
Gnomad NFE exome
AF:
0.178
Gnomad OTH exome
AF:
0.223
GnomAD4 exome
AF:
0.182
AC:
220123
AN:
1209678
Hom.:
23209
Cov.:
16
AF XY:
0.185
AC XY:
111842
AN XY:
605490
show subpopulations
Gnomad4 AFR exome
AF:
0.213
Gnomad4 AMR exome
AF:
0.176
Gnomad4 ASJ exome
AF:
0.157
Gnomad4 EAS exome
AF:
0.541
Gnomad4 SAS exome
AF:
0.257
Gnomad4 FIN exome
AF:
0.215
Gnomad4 NFE exome
AF:
0.161
Gnomad4 OTH exome
AF:
0.202
GnomAD4 genome
AF:
0.205
AC:
30686
AN:
149546
Hom.:
3561
Cov.:
31
AF XY:
0.208
AC XY:
15200
AN XY:
72998
show subpopulations
Gnomad4 AFR
AF:
0.221
Gnomad4 AMR
AF:
0.184
Gnomad4 ASJ
AF:
0.144
Gnomad4 EAS
AF:
0.557
Gnomad4 SAS
AF:
0.283
Gnomad4 FIN
AF:
0.214
Gnomad4 NFE
AF:
0.168
Gnomad4 OTH
AF:
0.203
Alfa
AF:
0.182
Hom.:
496
Bravo
AF:
0.203
Asia WGS
AF:
0.365
AC:
1258
AN:
3450

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
3.3
Dann
Benign
0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs12631786; hg19: chr3-132438719; API