19-33132368-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 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

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04051143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR88	NM_173479.4	c.199C>T	p.Pro67Ser	missense_variant	Exon 1 of 11	ENST00000355868.4	NP_775750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR88	ENST00000355868.4	c.199C>T	p.Pro67Ser	missense_variant	Exon 1 of 11	2	NM_173479.4	ENSP00000348129.2
WDR88	ENST00000361680.6	c.199C>T	p.Pro67Ser	missense_variant	Exon 1 of 12	1		ENSP00000355148.2
WDR88	ENST00000592765.5	c.199C>T	p.Pro67Ser	missense_variant	Exon 1 of 6	5		ENSP00000467383.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.199C>T (p.P67S) alteration is located in exon 1 (coding exon 1) of the WDR88 gene. This alteration results from a C to T substitution at nucleotide position 199, causing the proline (P) at amino acid position 67 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	.;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.42	.;N;N
REVEL	Benign	0.036
Sift	Benign	1.0	.;T;T
Sift4G	Benign	0.92	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.16
MutPred		0.39		Loss of catalytic residue at P67 (P = 0.0076);Loss of catalytic residue at P67 (P = 0.0076);Loss of catalytic residue at P67 (P = 0.0076);
MVP		0.067
MPC		0.26
ClinPred		0.074	T
GERP RS		-4.0
Varity_R		0.016
gMVP		0.060

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-33623274; COSMIC: COSV99404341; COSMIC: COSV99404341;