rs12631786

Variant names:

• chr3-132719875-T-C
• rs12631786
• NM_153240.5:c.394-45A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-132719875-T-C
• chr3-132719875-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153240.5(NPHP3):​c.394-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,359,224 control chromosomes in the GnomAD database, including 26,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3561 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23209 hom.)
• Consequence: NPHP3 NM_153240.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0210
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-132719875-T-C is Benign according to our data. Variant chr3-132719875-T-C is described in ClinVar as Benign. ClinVar VariationId is 262713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

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.394-45A>G		intron	N/A	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.498-45A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.394-45A>G		intron	N/A	ENSP00000338766.5	Q7Z494-1
	NPHP3	ENST00000971413.1		c.394-45A>G		intron	N/A	ENSP00000641472.1
	NPHP3	ENST00000971412.1		c.394-45A>G		intron	N/A	ENSP00000641471.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30681 AN: 149458 Hom.: 3564 Cov.: 31

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.227 AC: 41723 AN: 183714 AF XY: 0.227

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.568

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.182 AC: 220123 AN: 1209678 Hom.: 23209 Cov.: 16 AF XY: 0.185 AC XY: 111842 AN XY: 605490

African (AFR) AF: 0.213 AC: 5933 AN: 27860

American (AMR) AF: 0.176 AC: 6098 AN: 34646

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 3381 AN: 21564

East Asian (EAS) AF: 0.541 AC: 17608 AN: 32576

South Asian (SAS) AF: 0.257 AC: 17443 AN: 67806

European-Finnish (FIN) AF: 0.215 AC: 8712 AN: 40450

Middle Eastern (MID) AF: 0.233 AC: 848 AN: 3642

European-Non Finnish (NFE) AF: 0.161 AC: 150223 AN: 932144

Other (OTH) AF: 0.202 AC: 9877 AN: 48990

GnomAD4 genome AF: 0.205 AC: 30686 AN: 149546 Hom.: 3561 Cov.: 31 AF XY: 0.208 AC XY: 15200 AN XY: 72998

African (AFR) AF: 0.221 AC: 8876 AN: 40188

American (AMR) AF: 0.184 AC: 2776 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3464

East Asian (EAS) AF: 0.557 AC: 2855 AN: 5126

South Asian (SAS) AF: 0.283 AC: 1353 AN: 4780

European-Finnish (FIN) AF: 0.214 AC: 2122 AN: 9918

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11396 AN: 67706

Other (OTH) AF: 0.203 AC: 423 AN: 2080

Alfa AF: 0.183 Hom.: 509

Bravo AF: 0.203

Asia WGS AF: 0.365 AC: 1258 AN: 3450

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.35
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12631786; hg19: chr3-132438719;