3-149846069-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_183381.3(RNF13):c.43G>A(p.Val15Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000683 in 1,611,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V15D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RNF13
NM_183381.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.93

Publications

3 publications found

Variant links:

Genes affected

RNF13 (HGNC:10057): (ring finger protein 13) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. The specific function of this gene has not yet been determined. Alternatively spliced transcript variants that encode the same protein have been reported. A pseudogene, which is also located on chromosome 3, has been defined for this gene. [provided by RefSeq, Jul 2008]

RNF13 links:

ANKUB1 (HGNC:29642): (ankyrin repeat and ubiquitin domain containing 1)

ANKUB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0644137).

BP6

Variant 3-149846069-G-A is Benign according to our data. Variant chr3-149846069-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1518183.

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183381.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF13	NM_183381.3	MANE Select	c.43G>A	p.Val15Ile	missense	Exon 2 of 10	NP_899237.1	O43567-1
RNF13	NM_001378285.1		c.43G>A	p.Val15Ile	missense	Exon 3 of 11	NP_001365214.1	O43567-1
RNF13	NM_001378286.1		c.43G>A	p.Val15Ile	missense	Exon 2 of 10	NP_001365215.1	O43567-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF13	ENST00000392894.8	TSL:1 MANE Select	c.43G>A	p.Val15Ile	missense	Exon 2 of 10	ENSP00000376628.3	O43567-1
RNF13	ENST00000344229.7	TSL:1	c.43G>A	p.Val15Ile	missense	Exon 3 of 11	ENSP00000341361.3	O43567-1
RNF13	ENST00000910573.1		c.43G>A	p.Val15Ile	missense	Exon 2 of 11	ENSP00000580632.1

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251162

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460348

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726496

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33420

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4778

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111806

Other (OTH)

AF:

0.00

AC:

AN:

60266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000397

AC:

AN:

151164

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73792

show subpopulations

African (AFR)

AF:

0.000146

AC:

AN:

41034

American (AMR)

AF:

0.00

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5080

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67772

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0029

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

PhyloP100

3.9

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.070

REVEL

Benign

0.041

Sift

Benign

0.54

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.043

MVP

0.31

MPC

0.14

ClinPred

0.11

GERP RS

2.3

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.034

gMVP

0.24

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over