rs7193541

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018124.4(RFWD3):c.1690A>G(p.Ile564Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,613,106 control chromosomes in the GnomAD database, including 133,593 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.42 ( 14042 hom., cov: 32)

Exomes 𝑓: 0.40 ( 119551 hom. )

Consequence

RFWD3
NM_018124.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

Publications

65 publications found

Variant links:

Genes affected

RFWD3 (HGNC:25539): (ring finger and WD repeat domain 3) Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of DNA damage. Colocalizes with site of double-strand break. Implicated in Fanconi anemia. [provided by Alliance of Genome Resources, Apr 2022]

RFWD3 Gene-Disease associations (from GenCC):

Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia, complementation group W
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

RFWD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3153424E-4).

BP6

Variant 16-74630845-T-C is Benign according to our data. Variant chr16-74630845-T-C is described in ClinVar as Benign. ClinVar VariationId is 2124096.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFWD3	NM_018124.4 link	c.1690A>G	p.Ile564Val	missense_variant	Exon 10 of 13	ENST00000361070.9	NP_060594.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RFWD3	ENST00000361070.9 link	c.1690A>G	p.Ile564Val	missense_variant	Exon 10 of 13	1	NM_018124.4	ENSP00000354361.4	Q6PCD5
RFWD3	ENST00000571750.5 link	c.1690A>G	p.Ile564Val	missense_variant	Exon 11 of 14	2		ENSP00000460049.1	Q6PCD5
RFWD3	ENST00000575154.1 link	n.324A>G		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64063

AN:

151860

Hom.:

14033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.425

GnomAD2 exomes

AF:

0.370

AC:

92839

AN:

250638

AF XY:

0.367

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.436

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.396

GnomAD4 exome

AF:

0.399

AC:

583288

AN:

1461126

Hom.:

119551

Cov.:

AF XY:

0.394

AC XY:

286659

AN XY:

726858

show subpopulations

African (AFR)

AF:

0.511

AC:

17078

AN:

33430

American (AMR)

AF:

0.249

AC:

11125

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

9185

AN:

26122

East Asian (EAS)

AF:

0.371

AC:

14713

AN:

39644

South Asian (SAS)

AF:

0.237

AC:

20429

AN:

86188

European-Finnish (FIN)

AF:

0.344

AC:

18375

AN:

53400

Middle Eastern (MID)

AF:

0.450

AC:

2597

AN:

5766

European-Non Finnish (NFE)

AF:

0.419

AC:

465288

AN:

1111560

Other (OTH)

AF:

0.406

AC:

24498

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

17552

35104

52656

70208

87760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14178

28356

42534

56712

70890

<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:

0.422

AC:

64095

AN:

151980

Hom.:

14042

Cov.:

AF XY:

0.414

AC XY:

30753

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.508

AC:

21037

AN:

41434

American (AMR)

AF:

0.329

AC:

5021

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1217

AN:

3472

East Asian (EAS)

AF:

0.418

AC:

2155

AN:

5158

South Asian (SAS)

AF:

0.243

AC:

1172

AN:

4824

European-Finnish (FIN)

AF:

0.349

AC:

3677

AN:

10546

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28292

AN:

67962

Other (OTH)

AF:

0.426

AC:

897

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1881

3762

5643

7524

9405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.416

Hom.:

64535

Bravo

AF:

0.426

TwinsUK

AF:

0.419

AC:

1553

ALSPAC

AF:

0.418

AC:

1610

ESP6500AA

AF:

0.510

AC:

2240

ESP6500EA

AF:

0.423

AC:

3637

ExAC

AF:

0.381

AC:

46229

Asia WGS

AF:

0.358

AC:

1244

AN:

3478

EpiCase

AF:

0.411

EpiControl

AF:

0.422

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.1

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.76

.;T

MetaRNN

Benign

0.00023

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.23

N;N

PhyloP100

1.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.19

N;.

REVEL

Benign

0.037

Sift

Benign

0.47

T;.

Sift4G

Benign

0.57

T;T

Polyphen

0.0080

B;B

Vest4

0.061

ClinPred

0.0011

GERP RS

3.4

Varity_R

0.048

gMVP

0.14

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over