16-659001-C-T

Position:

• chr16-659001-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145294.5(WDR90):​c.3001C>T​(p.Pro1001Ser) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. P1001T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

Genes affected

WDR90 (HGNC:26960): (WD repeat domain 90) Involved in cilium assembly. Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

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=0.035989523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR90	NM_145294.5	c.3001C>T	p.Pro1001Ser	missense_variant	24/41	ENST00000293879.9	NP_660337.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR90	ENST00000293879.9	c.3001C>T	p.Pro1001Ser	missense_variant	24/41	5	NM_145294.5	ENSP00000293879.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.10
DANN	Benign	0.85
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.016
Sift	Benign	0.61	T;T
Sift4G	Benign	0.097	T;T
Polyphen		0.0	B;B
Vest4		0.043
MutPred		0.23		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.088
MPC		0.11
ClinPred		0.054	T
GERP RS		-9.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.088

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

LitVar

Other links and lift over

dbSNP: rs4984906; hg19: chr16-709001;