3-132681258-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153240.5(NPHP3):c.*651del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 105,728 control chromosomes in the GnomAD database, including 318 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (318 hom., cov: 23)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: NPHP3 NM_153240.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-132681258-CT-C is Benign according to our data. Variant chr3-132681258-CT-C is described in ClinVar as [Benign]. Clinvar id is 1259608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP3	NM_153240.5	c.*651del		3_prime_UTR_variant	27/27	ENST00000337331.10
NPHP3-ACAD11	NR_037804.1	n.3995+655del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHP3	ENST00000337331.10	c.*651del		3_prime_UTR_variant	27/27	1	NM_153240.5	P1
NPHP3	ENST00000474871.5	n.3843del		non_coding_transcript_exon_variant	11/11	2
NPHP3	ENST00000493732.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 9444 AN: 105646 Hom.: 320 Cov.: 23

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0952

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0930

GnomAD4 exome AF: 0.0135 AC: 1 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.0185 AC XY: 1 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: 0.0152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0893 AC: 9436 AN: 105654 Hom.: 318 Cov.: 23 AF XY: 0.0917 AC XY: 4507 AN XY: 49130

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0647

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0917

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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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;