Variant chr1-95244383-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015485.5(RWDD3):c.258T>G(p.Asn86Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,613,960 control chromosomes in the GnomAD database, including 603,401 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51859 hom., cov: 32)

Exomes 𝑓: 0.87 ( 551542 hom. )

Consequence

RWDD3
NM_015485.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.117

Variant links:

Genes affected

RWDD3 (HGNC:21393): (RWD domain containing 3) Involved in negative regulation of NF-kappaB transcription factor activity; positive regulation of hypoxia-inducible factor-1alpha signaling pathway; and positive regulation of protein sumoylation. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RWDD3 links:

TLCD4-RWDD3 (HGNC:):

TLCD4-RWDD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5616014E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RWDD3	NM_015485.5 linkuse as main transcript	c.258T>G	p.Asn86Lys	missense_variant	2/4	ENST00000370202.5
TLCD4-RWDD3	NM_001199691.1 linkuse as main transcript	c.*133T>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RWDD3	ENST00000370202.5 linkuse as main transcript	c.258T>G	p.Asn86Lys	missense_variant	2/4	3	NM_015485.5	P1	Q9Y3V2-1
	ENST00000630835.1 linkuse as main transcript	n.165-858A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.822

AC:

124990

AN:

151984

Hom.:

51836

Cov.:

show subpopulations

Gnomad AFR

AF:

0.717

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.936

Gnomad FIN

AF:

0.883

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.868

Gnomad OTH

AF:

0.842

GnomAD3 exomes

AF:

0.855

AC:

213310

AN:

249484

Hom.:

91632

AF XY:

0.862

AC XY:

116732

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.872

Gnomad EAS exome

AF:

0.775

Gnomad SAS exome

AF:

0.946

Gnomad FIN exome

AF:

0.876

Gnomad NFE exome

AF:

0.866

Gnomad OTH exome

AF:

0.868

GnomAD4 exome

AF:

0.868

AC:

1268515

AN:

1461858

Hom.:

551542

Cov.:

AF XY:

0.871

AC XY:

633206

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.709

Gnomad4 AMR exome

AF:

0.824

Gnomad4 ASJ exome

AF:

0.870

Gnomad4 EAS exome

AF:

0.803

Gnomad4 SAS exome

AF:

0.944

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.871

Gnomad4 OTH exome

AF:

0.861

GnomAD4 genome

AF:

0.822

AC:

125063

AN:

152102

Hom.:

51859

Cov.:

AF XY:

0.824

AC XY:

61277

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.716

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.876

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.936

Gnomad4 FIN

AF:

0.883

Gnomad4 NFE

AF:

0.868

Gnomad4 OTH

AF:

0.845

Alfa

AF:

0.859

Hom.:

135955

Bravo

AF:

0.811

TwinsUK

AF:

0.872

AC:

3232

ALSPAC

AF:

0.872

AC:

3362

ESP6500AA

AF:

0.722

AC:

2790

ESP6500EA

AF:

0.866

AC:

7172

ExAC

AF:

0.855

AC:

103244

Asia WGS

AF:

0.869

AC:

3022

AN:

3478

EpiCase

AF:

0.869

EpiControl

AF:

0.869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

DANN

Benign

0.49

DEOGEN2

Benign

0.0013

T;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.040

T;T

MetaRNN

Benign

0.0000026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.6

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

1.4

N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.036

MutPred

0.42

Gain of ubiquitination at N86 (P = 0.0138);Gain of ubiquitination at N86 (P = 0.0138);

MPC

0.13

ClinPred

0.0051

GERP RS

-1.5

Varity_R

0.034

gMVP

0.17

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