3-39065870-C-G

Variant names:

• chr3-39065870-C-G
• rs9840872
• NM_020839.4:c.249C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_001346227.2(WDR48):​c.-147C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,600,396 control chromosomes in the GnomAD database, including 2,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.069 (1174 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (946 hom.)
• Consequence: WDR48 NM_001346227.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.00700
• Publications: 4 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 3-39065870-C-G is Benign according to our data. Variant chr3-39065870-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060884.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346227.2. 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.249C>G	p.Leu83Leu	synonymous	Exon 3 of 19	NP_065890.1	Q8TAF3-1
	WDR48	NM_001346227.2		c.-147C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 18	NP_001333156.1
	WDR48	NM_001346225.2		c.249C>G	p.Leu83Leu	synonymous	Exon 3 of 20	NP_001333154.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR48	ENST00000302313.10	TSL:1 MANE Select	c.249C>G	p.Leu83Leu	synonymous	Exon 3 of 19	ENSP00000307491.5	Q8TAF3-1
	WDR48	ENST00000420940.6	TSL:1	n.249C>G		non_coding_transcript_exon	Exon 3 of 19	ENSP00000415963.2	F8W9K4
	WDR48	ENST00000925430.1		c.249C>G	p.Leu83Leu	synonymous	Exon 3 of 20	ENSP00000595489.1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10543 AN: 152086 Hom.: 1173 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0362

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.0612

GnomAD2 exomes AF: 0.0180 AC: 4317 AN: 239638 AF XY: 0.0133

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.0146

Gnomad ASJ exome AF: 0.00439

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00204

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.00762 AC: 11037 AN: 1448192 Hom.: 946 Cov.: 29 AF XY: 0.00670 AC XY: 4827 AN XY: 720214

African (AFR) AF: 0.228 AC: 7334 AN: 32160

American (AMR) AF: 0.0171 AC: 723 AN: 42234

Ashkenazi Jewish (ASJ) AF: 0.00484 AC: 125 AN: 25840

East Asian (EAS) AF: 0.0000511 AC: 2 AN: 39148

South Asian (SAS) AF: 0.000661 AC: 55 AN: 83262

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53126

Middle Eastern (MID) AF: 0.0163 AC: 93 AN: 5722

European-Non Finnish (NFE) AF: 0.00144 AC: 1592 AN: 1106870

Other (OTH) AF: 0.0186 AC: 1112 AN: 59830

GnomAD4 genome AF: 0.0695 AC: 10576 AN: 152204 Hom.: 1174 Cov.: 32 AF XY: 0.0680 AC XY: 5060 AN XY: 74432

African (AFR) AF: 0.234 AC: 9709 AN: 41480

American (AMR) AF: 0.0361 AC: 552 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00432 AC: 15 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00219 AC: 149 AN: 68024

Other (OTH) AF: 0.0605 AC: 128 AN: 2114

Alfa AF: 0.0203 Hom.: 92

Bravo AF: 0.0803

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	WDR48-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		-0.0070
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=288/12	polymorphism (auto)

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: rs9840872; hg19: chr3-39107361;