7-122698916-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PVS1_SupportingBS1BS2

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

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 19 codons. Genomic position: 122698864. Lost 0.049 part of the original CDS.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 185 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF133	NM_139175.2 link	c.3G>A	p.Met1?	start_lost	Exon 1 of 1	ENST00000340112.3	NP_631914.1	Q8WVZ7
CADPS2	NM_017954.11 link	c.454-35347G>A		intron_variant	Intron 2 of 29	ENST00000449022.7	NP_060424.9	Q86UW7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF133	ENST00000340112.3 link	c.3G>A	p.Met1?	start_lost	Exon 1 of 1	6	NM_139175.2	ENSP00000344489.2	Q8WVZ7
CADPS2	ENST00000449022.7 link	c.454-35347G>A		intron_variant	Intron 2 of 29	5	NM_017954.11	ENSP00000398481.2	Q86UW7-1
CADPS2	ENST00000412584.6 link	c.454-35347G>A		intron_variant	Intron 2 of 27	1		ENSP00000400401.2	Q86UW7-2
CADPS2	ENST00000313070.11 link	c.136-35347G>A		intron_variant	Intron 2 of 29	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

GnomAD2 exomes

AF:

0.0413

AC:

8611

AN:

208270

AF XY:

0.0411

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 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

African (AFR)

AF:

0.00471

AC:

151

AN:

32066

American (AMR)

AF:

0.0427

AC:

1632

AN:

38196

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

785

AN:

22804

East Asian (EAS)

AF:

0.0000761

AC:

AN:

39430

South Asian (SAS)

AF:

0.0195

AC:

1512

AN:

77474

European-Finnish (FIN)

AF:

0.106

AC:

5439

AN:

51150

Middle Eastern (MID)

AF:

0.0141

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.0405

AC:

44270

AN:

1091820

Other (OTH)

AF:

0.0316

AC:

1850

AN:

58526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2404

4808

7213

9617

12021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1556

3112

4668

6224

7780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0359

AC:

5464

AN:

152242

Hom.:

185

Cov.:

AF XY:

0.0366

AC XY:

2725

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00705

AC:

293

AN:

41554

American (AMR)

AF:

0.0322

AC:

492

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0328

AC:

114

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.0168

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.101

AC:

1075

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0491

AC:

3341

AN:

68010

Other (OTH)

AF:

0.0227

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

273

547

820

1094

1367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0384

Hom.:

321

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

(source)

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

PhyloP100

2.8

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

PromoterAI

0.019

Neutral

(source)

Varity_R

0.89

gMVP

0.32

Mutation Taster

=167/33

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over