4-183649555-T-A

Variant names:

• chr4-183649555-T-A
• rs756143023
• NM_152682.4:c.377A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152682.4(RWDD4):​c.377A>T​(p.Asn126Ile) 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. 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. N126S) 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: 1.62
• Publications: 0 publications found

Genes affected

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

ACMG classification

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=0.16226223).

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.377A>T	p.Asn126Ile	missense	Exon 5 of 8	NP_689895.2	Q6NW29-1
	RWDD4	NM_001307922.2		c.188A>T	p.Asn63Ile	missense	Exon 5 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.377A>T	p.Asn126Ile	missense	Exon 5 of 8	ENSP00000388920.2	Q6NW29-1
	RWDD4	ENST00000327570.13	TSL:3	c.377A>T	p.Asn126Ile	missense	Exon 5 of 7	ENSP00000332177.9	K4DI92
	RWDD4	ENST00000512740.1	TSL:5	c.188A>T	p.Asn63Ile	missense	Exon 4 of 7	ENSP00000423598.1	E7EV43

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.21
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.030
Sift	Benign	0.12	T
Sift4G	Benign	0.17	T
Polyphen		0.26	B
Vest4		0.41
MutPred		0.35		Gain of sheet (P = 0.0028)
MVP		0.59
MPC		0.46
ClinPred		0.24	T
GERP RS		2.6
Varity_R		0.14
gMVP		0.23
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756143023; hg19: chr4-184570708;