chr3-132681258-C-CT

Position:

• chr3-132681258-C-CT

Variant summary

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

The NM_153240.5(NPHP3):​c.*651_*652insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 105,608 control chromosomes in the GnomAD database, including 49 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (49 hom., cov: 23)
  • Exomes 𝑓: 0.027 (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-C-CT is Benign according to our data. Variant chr3-132681258-C-CT is described in ClinVar as [Benign]. Clinvar id is 1264737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP3	NM_153240.5	c.*651_*652insA		3_prime_UTR_variant	27/27	ENST00000337331.10	NP_694972.3
NPHP3-ACAD11	NR_037804.1	n.3995+655_3995+656insA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10	c.*651_*652insA		3_prime_UTR_variant	27/27	1	NM_153240.5	ENSP00000338766	P1
NPHP3	ENST00000474871.5	n.3843_3844insA		non_coding_transcript_exon_variant	11/11	2
NPHP3	ENST00000493732.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 2512 AN: 105526 Hom.: 48 Cov.: 23

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00969

Gnomad EAS AF: 0.00369

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.000715

Gnomad MID AF: 0.0155

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0204

GnomAD4 exome AF: 0.0270 AC: 2 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.0370 AC XY: 2 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: 0.500

GnomAD4 genome AF: 0.0238 AC: 2512 AN: 105534 Hom.: 49 Cov.: 23 AF XY: 0.0219 AC XY: 1076 AN XY: 49058

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00969

Gnomad4 EAS AF: 0.00370

Gnomad4 SAS AF: 0.00606

Gnomad4 FIN AF: 0.000715

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0203

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

Jun 04, 2021

- -

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;