RFWD3 p.Thr404Thr

Variant names:

• chr16-74636559-A-A
• NM_018124.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-74636560--
• chr16-74636560-C-A
• chr16-74636560-C-G
• chr16-74636560-C-T

Variant summary

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

The NM_018124.4(RFWD3):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RFWD3 NM_018124.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 0 publications found

Genes affected

RFWD3 (HGNC:25539): (ring finger and WD repeat domain 3) Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of DNA damage. Colocalizes with site of double-strand break. Implicated in Fanconi anemia. [provided by Alliance of Genome Resources, Apr 2022]

RFWD3 Gene-Disease associations (from GenCC):

• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia, complementation group W

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018124.4. 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
	RFWD3	NM_018124.4	MANE Select	c.		exon_region	Exon 8 of 13	NP_060594.3
	RFWD3	NM_001370534.1		c.		exon_region	Exon 8 of 13	NP_001357463.1	Q6PCD5
	RFWD3	NM_001370535.1		c.		exon_region	Exon 9 of 14	NP_001357464.1	Q6PCD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFWD3	ENST00000361070.9	TSL:1 MANE Select	c.		exon_region	Exon 8 of 13	ENSP00000354361.4	Q6PCD5
	RFWD3	ENST00000571750.5	TSL:2	c.		exon_region	Exon 9 of 14	ENSP00000460049.1	Q6PCD5
	RFWD3	ENST00000938436.1		c.		exon_region	Exon 10 of 15	ENSP00000608495.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.46

Splicing

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

hg19: chr16-74670457;