6-116584850-C-G

Position:

• chr6-116584850-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015952.4(RWDD1):​c.263C>G​(p.Ala88Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RWDD1 NM_015952.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

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]

ACMG classification

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=0.17719015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RWDD1	NM_015952.4	c.263C>G	p.Ala88Gly	missense_variant	3/7	ENST00000466444.7	NP_057036.2
RWDD1	NM_001007464.3	c.-26C>G		5_prime_UTR_variant	4/8		NP_001007465.1
RWDD1	NM_016104.4	c.-26C>G		5_prime_UTR_variant	5/9		NP_057188.2
RWDD1	XM_047418863.1	c.-26C>G		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	c.263C>G	p.Ala88Gly	missense_variant	3/7	1	NM_015952.4	ENSP00000420357	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

May 09, 2023

The c.263C>G (p.A88G) alteration is located in exon 3 (coding exon 3) of the RWDD1 gene. This alteration results from a C to G substitution at nucleotide position 263, causing the alanine (A) at amino acid position 88 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.046
Sift	Benign	0.35	T
Sift4G	Benign	0.38	T
Polyphen		0.010	B
Vest4		0.19
MutPred		0.45		Loss of ubiquitination at K85 (P = 0.0901);
MVP		0.45
MPC		0.35
ClinPred		0.54	D
GERP RS		3.5
Varity_R		0.11
gMVP		0.19

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

Other links and lift over

dbSNP: rs1443506927; hg19: chr6-116906013;