3-132681258-CTTTTTTTTTTTTT-CTTTTTTTTTTTTTTT

Variant names:

• chr3-132681258-C-CTT
• rs886058000
• NM_153240.5:c.*650_*651dupAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_153240.5(NPHP3):​c.*650_*651dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0049 (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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP3	NM_153240.5	c.*650_*651dupAA		3_prime_UTR_variant	Exon 27 of 27	ENST00000337331.10	NP_694972.3
NPHP3-ACAD11	NR_037804.1	n.3995+654_3995+655dupAA		intron_variant	Intron 26 of 44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331	c.*650_*651dupAA		3_prime_UTR_variant	Exon 27 of 27	1	NM_153240.5	ENSP00000338766.5
NPHP3-ACAD11	ENST00000632629.1	c.635+654_635+655dupAA		intron_variant	Intron 4 of 4	2		ENSP00000488520.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 515 AN: 105438 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.00540

Gnomad AMI AF: 0.0193

Gnomad AMR AF: 0.00305

Gnomad ASJ AF: 0.00431

Gnomad EAS AF: 0.00147

Gnomad SAS AF: 0.000335

Gnomad FIN AF: 0.000477

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00567

Gnomad OTH AF: 0.00282

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00488 AC: 515 AN: 105446 Hom.: 0 Cov.: 23 AF XY: 0.00473 AC XY: 232 AN XY: 49038

Gnomad4 AFR AF: 0.00540

Gnomad4 AMR AF: 0.00304

Gnomad4 ASJ AF: 0.00431

Gnomad4 EAS AF: 0.00147

Gnomad4 SAS AF: 0.000337

Gnomad4 FIN AF: 0.000477

Gnomad4 NFE AF: 0.00567

Gnomad4 OTH AF: 0.00281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886058000; hg19: chr3-132400102;