16-650073-C-T

Variant names:

• chr16-650073-C-T
• NM_145294.5:c.185C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145294.5(WDR90):​c.185C>T​(p.Thr62Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T62S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR90 NM_145294.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22763103).

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.185C>T	p.Thr62Ile	missense	Exon 3 of 41	NP_660337.3
	WDR90	NM_001438707.1		c.185C>T	p.Thr62Ile	missense	Exon 3 of 42	NP_001425636.1
	WDR90	NM_001438708.1		c.185C>T	p.Thr62Ile	missense	Exon 3 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.185C>T	p.Thr62Ile	missense	Exon 3 of 41	ENSP00000293879.4	Q96KV7-1
	WDR90	ENST00000420061.6	TSL:1	n.249C>T		non_coding_transcript_exon	Exon 3 of 17
	WDR90	ENST00000549648.5	TSL:1	n.249C>T		non_coding_transcript_exon	Exon 3 of 17

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.059
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.011	D
Polyphen		0.90	P
Vest4		0.46
MutPred		0.42		Loss of disorder (P = 0.0371)
MVP		0.17
MPC		0.46
ClinPred		0.92	D
GERP RS		2.5
Varity_R		0.22
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-700073;