rs202142404

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_153240.5(NPHP3):c.233G>T(p.Gly78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,606,008 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G78G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

NPHP3
NM_153240.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:9

Conservation

PhyloP100: 3.18

Publications

1 publications found

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]

NPHP3 links:

NPHP3-AS1 (HGNC:24129): (NPHP3 antisense RNA 1)

NPHP3-AS1 links:

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]

NPHP3-ACAD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37433177).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NPHP3	NM_153240.5	MANE Select	c.233G>T	p.Gly78Val	missense	Exon 1 of 27	NP_694972.3
NPHP3-AS1	NR_002811.2		n.374C>A		non_coding_transcript_exon	Exon 1 of 11
NPHP3-ACAD11	NR_037804.1		n.337G>T		non_coding_transcript_exon	Exon 1 of 45

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.233G>T	p.Gly78Val	missense	Exon 1 of 27	ENSP00000338766.5
NPHP3	ENST00000383282.3	TSL:1	c.233G>T	p.Gly78Val	missense	Exon 1 of 2	ENSP00000372769.2
NPHP3-AS1	ENST00000489343.5	TSL:1	n.374C>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000545

AC:

AN:

238492

AF XY:

0.0000609

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000567

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000729

AC:

106

AN:

1453822

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

723664

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39508

South Asian (SAS)

AF:

0.00

AC:

AN:

86130

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000927

AC:

103

AN:

1111302

Other (OTH)

AF:

0.0000332

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000498

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephronophthisis (2)

not provided (2)

Inborn genetic diseases (1)

Meckel-Gruber syndrome (1)

Nephronophthisis 3;C2673885:NPHP3-related Meckel-like syndrome;C3715199:Renal-hepatic-pancreatic dysplasia 1 (1)

NPHP3-related disorder (1)

Renal-hepatic-pancreatic dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.37

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.69

PhyloP100

3.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.20

REVEL

Uncertain

0.33

Sift

Benign

0.14

Sift4G

Benign

0.14

Polyphen

0.22

Vest4

0.25

MutPred

0.26

Gain of glycosylation at S80 (P = 0.0268)

MVP

0.87

MPC

0.28

ClinPred

0.21

GERP RS

2.8

PromoterAI

-0.0061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.42

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over