NM_153240.5:c.3697-7delT

Variant names:

• chr3-132682824-TA-T
• rs564013823
• NM_153240.5:c.3697-7delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_153240.5(NPHP3):​c.3697-7delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000711 in 1,557,810 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (9 hom.)
• Consequence: NPHP3 NM_153240.5 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.497
• 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-132682824-TA-T is Benign according to our data. Variant chr3-132682824-TA-T is described in ClinVar as Benign. ClinVar VariationId is 422589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000664 (101/152110) while in subpopulation EAS AF = 0.0129 (67/5190). AF 95% confidence interval is 0.0104. There are 0 homozygotes in GnomAd4. There are 55 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.3697-7delT		splice_region intron	N/A	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.3703-7delT		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.3697-7delT		splice_region intron	N/A	ENSP00000338766.5	Q7Z494-1
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.343-7delT		splice_region intron	N/A	ENSP00000488520.1	A0A0J9YXS1
	NPHP3	ENST00000971413.1		c.3496-7delT		splice_region intron	N/A	ENSP00000641472.1

Frequencies

GnomAD3 genomes AF: 0.000665 AC: 101 AN: 151992 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00155 AC: 388 AN: 250424 AF XY: 0.00169

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.0158

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.000433

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.000716 AC: 1007 AN: 1405700 Hom.: 9 Cov.: 24 AF XY: 0.000777 AC XY: 546 AN XY: 702600

African (AFR) AF: 0.0000309 AC: 1 AN: 32376

American (AMR) AF: 0.0000224 AC: 1 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.000155 AC: 4 AN: 25802

East Asian (EAS) AF: 0.0157 AC: 616 AN: 39318

South Asian (SAS) AF: 0.000765 AC: 65 AN: 85000

European-Finnish (FIN) AF: 0.000581 AC: 31 AN: 53352

Middle Eastern (MID) AF: 0.000885 AC: 5 AN: 5648

European-Non Finnish (NFE) AF: 0.000229 AC: 243 AN: 1061046

Other (OTH) AF: 0.000701 AC: 41 AN: 58506

GnomAD4 genome AF: 0.000664 AC: 101 AN: 152110 Hom.: 0 Cov.: 33 AF XY: 0.000740 AC XY: 55 AN XY: 74354

African (AFR) AF: 0.000120 AC: 5 AN: 41504

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5190

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000436 Hom.: 1

Bravo AF: 0.000782

Asia WGS AF: 0.00780 AC: 27 AN: 3476

EpiCase AF: 0.000273

EpiControl AF: 0.000475

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Nephronophthisis (1)
-	-	1	not provided (1)
-	-	1	NPHP3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: 34

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

Other links and lift over

dbSNP: rs564013823; hg19: chr3-132401668; COSMIC: COSV53904964; COSMIC: COSV53904964;