1-95244383-T-C

Variant names:

• chr1-95244383-T-C
• rs2296308
• NM_015485.5:c.258T>C
• RWDD3 p.Asn86Asn

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015485.5(RWDD3):​c.258T>C​(p.Asn86Asn) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RWDD3 NM_015485.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 40 publications found

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]

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]

ENSG00000228852 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD3	NM_015485.5	MANE Select	c.258T>C	p.Asn86Asn	synonymous	Exon 2 of 4	NP_056300.3	Q9Y3V2-1
	RWDD3	NM_001278248.2		c.213T>C	p.Asn71Asn	synonymous	Exon 3 of 5	NP_001265177.2
	RWDD3	NM_001199682.2		c.258T>C	p.Asn86Asn	synonymous	Exon 2 of 4	NP_001186611.2	Q9Y3V2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD3	ENST00000370202.5	TSL:3 MANE Select	c.258T>C	p.Asn86Asn	synonymous	Exon 2 of 4	ENSP00000359221.4	Q9Y3V2-1
	RWDD3	ENST00000263893.10	TSL:1	c.258T>C	p.Asn86Asn	synonymous	Exon 2 of 3	ENSP00000263893.6	Q9Y3V2-2
	TLCD4-RWDD3	ENST00000604534.5	TSL:2	c.*133T>C		3_prime_UTR	Exon 8 of 8	ENSP00000475025.1	S4R434

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.44
PhyloP100		-0.12
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2296308;

hg19: chr1-95709939;