rs142663818

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153240.5(NPHP3):c.449C>T(p.Ala150Val) variant causes a missense change. The variant allele was found at a frequency of 0.00094 in 1,599,856 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A150T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 14 hom. )

Consequence

NPHP3
NM_153240.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 6.74

Publications

6 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-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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010195643).

BP6

Variant 3-132719775-G-A is Benign according to our data. Variant chr3-132719775-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 241998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00136 (207/151676) while in subpopulation EAS AF = 0.0186 (96/5162). AF 95% confidence interval is 0.0156. There are 0 homozygotes in GnomAd4. There are 111 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	NM_153240.5	MANE Select	c.449C>T	p.Ala150Val	missense	Exon 2 of 27	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.553C>T		non_coding_transcript_exon	Exon 2 of 45

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.449C>T	p.Ala150Val	missense	Exon 2 of 27	ENSP00000338766.5	Q7Z494-1
NPHP3	ENST00000971413.1		c.449C>T	p.Ala150Val	missense	Exon 2 of 25	ENSP00000641472.1
NPHP3	ENST00000971412.1		c.449C>T	p.Ala150Val	missense	Exon 2 of 23	ENSP00000641471.1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

208

AN:

151566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0186

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00170

AC:

423

AN:

249394

AF XY:

0.00162

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000896

AC:

1297

AN:

1448180

Hom.:

Cov.:

AF XY:

0.000911

AC XY:

656

AN XY:

720470

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

33282

American (AMR)

AF:

0.000181

AC:

AN:

44234

Ashkenazi Jewish (ASJ)

AF:

0.00120

AC:

AN:

25804

East Asian (EAS)

AF:

0.0224

AC:

880

AN:

39240

South Asian (SAS)

AF:

0.00121

AC:

102

AN:

84222

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52766

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000825

AC:

AN:

1103214

Other (OTH)

AF:

0.00166

AC:

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00136

AC:

207

AN:

151676

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

111

AN XY:

74140

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

41376

American (AMR)

AF:

0.000131

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.0186

AC:

AN:

5162

South Asian (SAS)

AF:

0.00145

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000133

AC:

AN:

67912

Other (OTH)

AF:

0.00190

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00118

Hom.:

Bravo

AF:

0.00177

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00177

AC:

215

Asia WGS

AF:

0.00927

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Kidney disorder (1)

Nephronophthisis (1)

Nephronophthisis 3 (1)

NPHP3-related Meckel-like syndrome (1)

Renal-hepatic-pancreatic dysplasia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.60

MutationAssessor

Benign

0.81

PhyloP100

6.7

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.97

REVEL

Uncertain

0.48

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.72

MVP

0.94

MPC

0.51

ClinPred

0.018

GERP RS

5.5

Varity_R

0.33

gMVP

0.29

Mutation Taster

=65/35

polymorphism

(source)

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

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