3-132681258-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTT

Variant names:

• chr3-132681258-C-CTTT
• rs886058000
• NM_153240.5:c.*649_*651dupAAA

Variant summary

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

The NM_153240.5(NPHP3):​c.*649_*651dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 105,562 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00054 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPHP3 NM_153240.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

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-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]

ACMG classification

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.*649_*651dupAAA		3_prime_UTR	Exon 27 of 27	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.3995+653_3995+655dupAAA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.*649_*651dupAAA		3_prime_UTR	Exon 27 of 27	ENSP00000338766.5	Q7Z494-1
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.635+653_635+655dupAAA		intron	N/A	ENSP00000488520.1	A0A0J9YXS1
	NPHP3	ENST00000971413.1		c.*649_*651dupAAA		splice_region	Exon 25 of 25	ENSP00000641472.1

Frequencies

GnomAD3 genomes AF: 0.000540 AC: 57 AN: 105554 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000616

Gnomad AMI AF: 0.00148

Gnomad AMR AF: 0.0000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000736

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000238

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000644

Gnomad OTH AF: 0.000704

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.000540 AC: 57 AN: 105562 Hom.: 0 Cov.: 23 AF XY: 0.000652 AC XY: 32 AN XY: 49082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000615 AC: 17 AN: 27636

American (AMR) AF: 0.0000980 AC: 1 AN: 10202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2786

East Asian (EAS) AF: 0.000737 AC: 2 AN: 2712

South Asian (SAS) AF: 0.00 AC: 0 AN: 2968

European-Finnish (FIN) AF: 0.000238 AC: 1 AN: 4196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.000644 AC: 34 AN: 52784

Other (OTH) AF: 0.000700 AC: 1 AN: 1428

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs886058000; hg19: chr3-132400102;