16-659001-C-T

Variant names:

• chr16-659001-C-T
• rs4984906
• NM_145294.5:c.3001C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 38 publications found

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

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=0.035989523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145294.5. 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
	WDR90	NM_145294.5	MANE Select	c.3001C>T	p.Pro1001Ser	missense	Exon 24 of 41	NP_660337.3
	WDR90	NM_001438707.1		c.3004C>T	p.Pro1002Ser	missense	Exon 24 of 42	NP_001425636.1
	WDR90	NM_001438708.1		c.3001C>T	p.Pro1001Ser	missense	Exon 24 of 42	NP_001425637.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR90	ENST00000293879.9	TSL:5 MANE Select	c.3001C>T	p.Pro1001Ser	missense	Exon 24 of 41	ENSP00000293879.4	Q96KV7-1
	WDR90	ENST00000552943.5	TSL:1	n.5083C>T		non_coding_transcript_exon	Exon 21 of 26
	WDR90	ENST00000909862.1		c.3001C>T	p.Pro1001Ser	missense	Exon 24 of 42	ENSP00000579921.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.60
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.016
Sift	Benign	0.61	T
Sift4G	Benign	0.097	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.23		Gain of sheet (P = 0.0344)
MVP		0.088
MPC		0.11
ClinPred		0.054	T
GERP RS		-9.6
PromoterAI		0.024	Neutral
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

Other links and lift over

dbSNP: rs4984906; hg19: chr16-709001;