3-132681258-CTT-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_153240.5(NPHP3):​c.*650_*651del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 105,186 control chromosomes in the GnomAD database, including 200 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.089 ( 200 hom., cov: 23)
Exomes 𝑓: 0.027 ( 0 hom. )

Consequence

NPHP3
NM_153240.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.19
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 -8 ACMG points.

BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NPHP3NM_153240.5 linkuse as main transcriptc.*650_*651del 3_prime_UTR_variant 27/27 ENST00000337331.10 NP_694972.3
NPHP3-ACAD11NR_037804.1 linkuse as main transcriptn.3995+654_3995+655del intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NPHP3ENST00000337331.10 linkuse as main transcriptc.*650_*651del 3_prime_UTR_variant 27/271 NM_153240.5 ENSP00000338766 P1Q7Z494-1
NPHP3ENST00000474871.5 linkuse as main transcriptn.3842_3843del non_coding_transcript_exon_variant 11/112
NPHP3ENST00000493732.5 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0890
AC:
9350
AN:
105104
Hom.:
200
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.0267
Gnomad AMI
AF:
0.0519
Gnomad AMR
AF:
0.112
Gnomad ASJ
AF:
0.148
Gnomad EAS
AF:
0.123
Gnomad SAS
AF:
0.121
Gnomad FIN
AF:
0.0995
Gnomad MID
AF:
0.119
Gnomad NFE
AF:
0.110
Gnomad OTH
AF:
0.108
GnomAD4 exome
AF:
0.0270
AC:
2
AN:
74
Hom.:
0
AF XY:
0.0370
AC XY:
2
AN XY:
54
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0152
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.0889
AC:
9348
AN:
105112
Hom.:
200
Cov.:
23
AF XY:
0.0897
AC XY:
4386
AN XY:
48914
show subpopulations
Gnomad4 AFR
AF:
0.0267
Gnomad4 AMR
AF:
0.112
Gnomad4 ASJ
AF:
0.148
Gnomad4 EAS
AF:
0.123
Gnomad4 SAS
AF:
0.121
Gnomad4 FIN
AF:
0.0995
Gnomad4 NFE
AF:
0.110
Gnomad4 OTH
AF:
0.107

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Renal-hepatic-pancreatic dysplasia 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Meckel-Gruber syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs886058000; hg19: chr3-132400102; API