Genetic Variant NM_015485.5:c.149C>A (chr1-95244274-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015485.5(RWDD3):c.149C>A(p.Pro50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RWDD3
NM_015485.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.916

Publications

0 publications found

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:49388): (TLCD4-RWDD3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM56 (transmembrane protein 56) and RWDD3 (RWD domain containing 3) genes on chromosome 1. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

TLCD4-RWDD3 links:

ENSG00000228852 (HGNC:):

ENSG00000228852 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.119818896).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015485.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RWDD3	NM_015485.5	MANE Select	c.149C>A	p.Pro50His	missense	Exon 2 of 4	NP_056300.3	Q9Y3V2-1
RWDD3	NM_001278248.2		c.104C>A	p.Pro35His	missense	Exon 3 of 5	NP_001265177.2
RWDD3	NM_001199682.2		c.149C>A	p.Pro50His	missense	Exon 2 of 4	NP_001186611.2	Q9Y3V2-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RWDD3	ENST00000370202.5	TSL:3 MANE Select	c.149C>A	p.Pro50His	missense	Exon 2 of 4	ENSP00000359221.4	Q9Y3V2-1
RWDD3	ENST00000263893.10	TSL:1	c.149C>A	p.Pro50His	missense	Exon 2 of 3	ENSP00000263893.6	Q9Y3V2-2
TLCD4-RWDD3	ENST00000604534.5	TSL:2	c.*24C>A		3_prime_UTR	Exon 8 of 8	ENSP00000475025.1	S4R434

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249522

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.57

M_CAP

Benign

0.0056

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.92

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

REVEL

Benign

0.10

Sift

Benign

0.17

Sift4G

Benign

0.36

Polyphen

0.072

Vest4

0.21

MutPred

0.43

Gain of sheet (P = 0.0266)

MVP

0.63

MPC

0.17

ClinPred

0.23

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.093

gMVP

0.36

Mutation Taster

=74/26

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over