chr19-33132368-C-T

Variant names:

• chr19-33132368-C-T
• NM_173479.4:c.199C>T

Variant summary

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

The NM_173479.4(WDR88):​c.199C>T​(p.Pro67Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: WDR88 NM_173479.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.54
• Publications: 0 publications found

Genes affected

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

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 (MetaRNN=0.04051143).

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.199C>T	p.Pro67Ser	missense	Exon 1 of 11	NP_775750.3
	WDR88	NR_135565.2		n.255C>T		non_coding_transcript_exon	Exon 1 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR88	ENST00000355868.4	TSL:2 MANE Select	c.199C>T	p.Pro67Ser	missense	Exon 1 of 11	ENSP00000348129.2	Q6ZMY6-1
	WDR88	ENST00000361680.6	TSL:1	c.199C>T	p.Pro67Ser	missense	Exon 1 of 12	ENSP00000355148.2	Q6ZMY6-2
	WDR88	ENST00000592765.5	TSL:5	c.199C>T	p.Pro67Ser	missense	Exon 1 of 6	ENSP00000467383.1	K7EPH1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

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	Benign	0.074
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0010
DANN	Benign	0.85
DEOGEN2	Benign	0.00096	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-3.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.92	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.39		Loss of catalytic residue at P67 (P = 0.0076)
MVP		0.067
MPC		0.26
ClinPred		0.074	T
GERP RS		-4.0
PromoterAI		-0.040	Neutral
Varity_R		0.016
gMVP		0.060
Mutation Taster		=98/2	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: chr19-33623274; COSMIC: COSV99404341; COSMIC: COSV99404341;