3-39077164-C-G

Variant names:

• chr3-39077164-C-G
• rs144605947
• NM_020839.4:c.923C>G

Variant summary

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

The NM_020839.4(WDR48):​c.923C>G​(p.Pro308Arg) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P308L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR48 NM_020839.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 0 publications found

Genes affected

WDR48 (HGNC:30914): (WD repeat domain 48) The protein encoded by this gene has been shown to interact with ubiquitin specific peptidase 1 (USP1), activating the deubiquitinating activity of USP1 and allowing it to remove the ubiquitin moiety from monoubiquitinated FANCD2. FANCD2 is ubiquitinated in response to DNA damage. [provided by RefSeq, Sep 2016]

WDR48 Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 60

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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_020839.4. 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
	WDR48	NM_020839.4	MANE Select	c.923C>G	p.Pro308Arg	missense	Exon 9 of 19	NP_065890.1	Q8TAF3-1
	WDR48	NM_001346225.2		c.1037C>G	p.Pro346Arg	missense	Exon 10 of 20	NP_001333154.1
	WDR48	NM_001303403.2		c.896C>G	p.Pro299Arg	missense	Exon 9 of 19	NP_001290332.1	Q8TAF3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR48	ENST00000302313.10	TSL:1 MANE Select	c.923C>G	p.Pro308Arg	missense	Exon 9 of 19	ENSP00000307491.5	Q8TAF3-1
	WDR48	ENST00000420940.6	TSL:1	n.*430C>G		non_coding_transcript_exon	Exon 8 of 19	ENSP00000415963.2	F8W9K4
	WDR48	ENST00000420940.6	TSL:1	n.*430C>G		3_prime_UTR	Exon 8 of 19	ENSP00000415963.2	F8W9K4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.18	N
REVEL	Uncertain	0.30
Sift	Benign	0.33	T
Sift4G	Benign	0.54	T
Polyphen		1.0	D
Vest4		0.74
MutPred		0.41		Loss of glycosylation at P310 (P = 0.0213)
MVP		0.18
MPC		0.013
ClinPred		0.78	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.44
Mutation Taster		=172/128	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

Other links and lift over

dbSNP: rs144605947; hg19: chr3-39118655;