Variant 6-116584839-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015952.4(RWDD1):c.252A>T(p.Leu84Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,589,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RWDD1
NM_015952.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

RWDD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20660546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RWDD1	NM_015952.4 linkuse as main transcript	c.252A>T	p.Leu84Phe	missense_variant	3/7	ENST00000466444.7	NP_057036.2
RWDD1	NM_001007464.3 linkuse as main transcript	c.-37A>T		5_prime_UTR_variant	4/8		NP_001007465.1
RWDD1	NM_016104.4 linkuse as main transcript	c.-37A>T		5_prime_UTR_variant	5/9		NP_057188.2
RWDD1	XM_047418863.1 linkuse as main transcript	c.-37A>T		5_prime_UTR_variant	5/9		XP_047274819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RWDD1	ENST00000466444.7 linkuse as main transcript	c.252A>T	p.Leu84Phe	missense_variant	3/7	1	NM_015952.4	ENSP00000420357	P1	Q9H446-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.000478

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

249988

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1436854

Hom.:

Cov.:

AF XY:

0.00000977

AC XY:

AN XY:

716358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000367

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000907

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.252A>T (p.L84F) alteration is located in exon 3 (coding exon 3) of the RWDD1 gene. This alteration results from a A to T substitution at nucleotide position 252, causing the leucine (L) at amino acid position 84 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

Eigen

Benign

-0.049

Eigen_PC

Benign

0.030

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.73

M_CAP

Benign

0.022

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.95

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.2

REVEL

Benign

0.23

Sift

Benign

0.14

Sift4G

Benign

0.11

Polyphen

0.035

Vest4

0.42

MutPred

0.56

Loss of stability (P = 0.0595);

MVP

0.39

MPC

0.37

ClinPred

0.22

GERP RS

3.3

Varity_R

0.079

gMVP

0.48

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over