4-183646526-C-G

Position:

• chr4-183646526-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152682.4(RWDD4):​c.493G>C​(p.Glu165Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RWDD4 NM_152682.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

Genes affected

RWDD4 (HGNC:23750): (RWD domain containing 4)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RWDD4	NM_152682.4	c.493G>C	p.Glu165Gln	missense_variant	6/8	ENST00000326397.10	NP_689895.2
RWDD4	NM_001307922.2	c.304G>C	p.Glu102Gln	missense_variant	6/8		NP_001294851.1
RWDD4	XM_047449747.1	c.469G>C	p.Glu157Gln	missense_variant	6/8		XP_047305703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RWDD4	ENST00000326397.10	c.493G>C	p.Glu165Gln	missense_variant	6/8	2	NM_152682.4	ENSP00000388920	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459468 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.493G>C (p.E165Q) alteration is located in exon 6 (coding exon 6) of the RWDD4 gene. This alteration results from a G to C substitution at nucleotide position 493, causing the glutamic acid (E) at amino acid position 165 to be replaced by a glutamine (Q). 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	0.28
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.7	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N;N;D;D
REVEL	Benign	0.14
Sift	Benign	0.054	T;T;D;D
Sift4G	Uncertain	0.056	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.63
MutPred		0.23		Gain of glycosylation at T160 (P = 0.0246);Gain of glycosylation at T160 (P = 0.0246);.;.;
MVP		0.75
MPC		0.95
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.32
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-184567679;