Variant chr7-122698916-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1BS1BS2

The NM_139175.2(RNF133):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,569,222 control chromosomes in the GnomAD database, including 1,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.036 ( 185 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1475 hom. )

Consequence

RNF133
NM_139175.2 start_lost

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

RNF133 (HGNC:21154): (ring finger protein 133) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene has no intron. [provided by RefSeq, Jul 2008]

RNF133 links:

CADPS2 (HGNC:16018): (calcium dependent secretion activator 2) This gene encodes a member of the calcium-dependent activator of secretion (CAPS) protein family, which are calcium binding proteins that regulate the exocytosis of synaptic and dense-core vesicles in neurons and neuroendocrine cells. Mutations in this gene may contribute to autism susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

CADPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0359 (5464/152242) while in subpopulation NFE AF= 0.0491 (3341/68010). AF 95% confidence interval is 0.0477. There are 185 homozygotes in gnomad4. There are 2725 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 185 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF133	NM_139175.2 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/1	ENST00000340112.3	NP_631914.1	Q8WVZ7
CADPS2	NM_017954.11 linkuse as main transcript	c.454-35347G>A		intron_variant		ENST00000449022.7	NP_060424.9	Q86UW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF133	ENST00000340112.3 linkuse as main transcript	c.3G>A	p.Met1?	start_lost	1/1	6	NM_139175.2	ENSP00000344489.2	Q8WVZ7
CADPS2	ENST00000449022.7 linkuse as main transcript	c.454-35347G>A		intron_variant		5	NM_017954.11	ENSP00000398481.2	Q86UW7-1
CADPS2	ENST00000412584.6 linkuse as main transcript	c.454-35347G>A		intron_variant		1		ENSP00000400401.2	Q86UW7-2
CADPS2	ENST00000313070.11 linkuse as main transcript	c.136-35347G>A		intron_variant		5		ENSP00000325581.8	F8W8P5

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5468

AN:

152124

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00707

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0324

Gnomad ASJ

AF:

0.0328

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0491

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0413

AC:

8611

AN:

208270

Hom.:

250

AF XY:

0.0411

AC XY:

4589

AN XY:

111536

show subpopulations

Gnomad AFR exome

AF:

0.00639

Gnomad AMR exome

AF:

0.0468

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.0203

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0446

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0393

AC:

55720

AN:

1416980

Hom.:

1475

Cov.:

AF XY:

0.0390

AC XY:

27347

AN XY:

701212

show subpopulations

Gnomad4 AFR exome

AF:

0.00471

Gnomad4 AMR exome

AF:

0.0427

Gnomad4 ASJ exome

AF:

0.0344

Gnomad4 EAS exome

AF:

0.0000761

Gnomad4 SAS exome

AF:

0.0195

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.0405

Gnomad4 OTH exome

AF:

0.0316

GnomAD4 genome

AF:

0.0359

AC:

5464

AN:

152242

Hom.:

185

Cov.:

AF XY:

0.0366

AC XY:

2725

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0328

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0491

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0392

Hom.:

194

Bravo

AF:

0.0279

TwinsUK

AF:

0.0364

AC:

135

ALSPAC

AF:

0.0374

AC:

144

ESP6500AA

AF:

0.00659

AC:

ESP6500EA

AF:

0.0425

AC:

363

ExAC

AF:

0.0388

AC:

4696

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0070

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.4

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.046

Vest4

0.33

MutPred

0.97

Loss of disorder (P = 0.0682);

ClinPred

0.067

GERP RS

4.8

Varity_R

0.89

gMVP

0.32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over