19-33137718-C-A

Variant names:

• chr19-33137718-C-A
• NM_173479.4:c.318C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173479.4(WDR88):​c.318C>A​(p.Ser106Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR88 NM_173479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.42
• Publications: 0 publications found

Genes affected

WDR88 (HGNC:26999): (WD repeat domain 88)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173479.4. 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
	WDR88	NM_173479.4	MANE Select	c.318C>A	p.Ser106Arg	missense	Exon 2 of 11	NP_775750.3
	WDR88	NR_135565.2		n.374C>A		non_coding_transcript_exon	Exon 2 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR88	ENST00000355868.4	TSL:2 MANE Select	c.318C>A	p.Ser106Arg	missense	Exon 2 of 11	ENSP00000348129.2	Q6ZMY6-1
	WDR88	ENST00000361680.6	TSL:1	c.318C>A	p.Ser106Arg	missense	Exon 2 of 12	ENSP00000355148.2	Q6ZMY6-2
	WDR88	ENST00000592765.5	TSL:5	c.318C>A	p.Ser106Arg	missense	Exon 2 of 6	ENSP00000467383.1	K7EPH1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.21	N
PhyloP100		-1.4
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.98	D
Vest4		0.75
MutPred		0.53		Gain of methylation at S106 (P = 0.102)
MVP		0.072
MPC		0.94
ClinPred		0.96	D
GERP RS		-2.2
Varity_R		0.37
gMVP		0.45
Mutation Taster		=91/9	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

hg19: chr19-33628624;