rs371595803

Variant names:

• chr4-183651237-C-G
• rs371595803
• NM_152682.4:c.196G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-183651237-C-G
• chr4-183651237-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152682.4(RWDD4):​c.196G>C​(p.Ala66Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A66T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RWDD4 NM_152682.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152682.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD4	NM_152682.4	MANE Select	c.196G>C	p.Ala66Pro	missense	Exon 3 of 8	NP_689895.2	Q6NW29-1
	RWDD4	NM_001307922.2		c.7G>C	p.Ala3Pro	missense	Exon 3 of 8	NP_001294851.1	E7EV43

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD4	ENST00000326397.10	TSL:2 MANE Select	c.196G>C	p.Ala66Pro	missense	Exon 3 of 8	ENSP00000388920.2	Q6NW29-1
	RWDD4	ENST00000327570.13	TSL:3	c.196G>C	p.Ala66Pro	missense	Exon 3 of 7	ENSP00000332177.9	K4DI92
	RWDD4	ENST00000512740.1	TSL:5	c.7G>C	p.Ala3Pro	missense	Exon 2 of 7	ENSP00000423598.1	E7EV43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.026	D
Sift4G	Benign	0.065	T
Polyphen		1.0	D
Vest4		0.89
MVP		0.75
MPC		1.1
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.77
gMVP		0.86
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371595803; hg19: chr4-184572390;