Genetic Variant NPHP3:c.*640_*651delAAAAAAAAAAAA (chr3-132681258-CTTTTTTTTTTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_153240.5(NPHP3):c.*640_*651delAAAAAAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 105,594 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NPHP3
NM_153240.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.640_651delAAAAAAAAAAAA		3_prime_UTR	Exon 27 of 27	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.3995+644_3995+655delAAAAAAAAAAAA		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.640_651delAAAAAAAAAAAA	3_prime_UTR	Exon 27 of 27	ENSP00000338766.5	Q7Z494-1
NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.635+644_635+655delAAAAAAAAAAAA	intron	N/A	ENSP00000488520.1	A0A0J9YXS1
NPHP3	ENST00000971413.1		c.640_651delAAAAAAAAAAAA	splice_region	Exon 25 of 25	ENSP00000641472.1

Frequencies

GnomAD3 genomes

AF:

0.0000758

AC:

AN:

105586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000294

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:

0.0000947

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0000758

AC:

AN:

105594

Hom.:

Cov.:

AF XY:

0.0000611

AC XY:

AN XY:

49096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27640

American (AMR)

AF:

0.000294

AC:

AN:

10204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2788

East Asian (EAS)

AF:

0.00

AC:

AN:

2716

South Asian (SAS)

AF:

0.00

AC:

AN:

2968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

178

European-Non Finnish (NFE)

AF:

0.0000947

AC:

AN:

52802

Other (OTH)

AF:

0.00

AC:

AN:

1428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.00

Hom.:

Bravo

AF:

0.0000680

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over