16-659001-C-A

Position:

• chr16-659001-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145294.5(WDR90):​c.3001C>A​(p.Pro1001Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,612,822 control chromosomes in the GnomAD database, including 169,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.55 (26232 hom., cov: 33)
  • Exomes 𝑓: 0.42 (143079 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2617623E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR90	NM_145294.5	c.3001C>A	p.Pro1001Thr	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>A	p.Pro1001Thr	missense_variant	24/41	5	NM_145294.5	ENSP00000293879.4

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83028 AN: 151918 Hom.: 26176 Cov.: 33

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.477

GnomAD3 exomes AF: 0.523 AC: 130041 AN: 248430 Hom.: 39375 AF XY: 0.506 AC XY: 68384 AN XY: 135074

Gnomad AFR exome AF: 0.839

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.984

Gnomad SAS exome AF: 0.560

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.419 AC: 611854 AN: 1460786 Hom.: 143079 Cov.: 56 AF XY: 0.420 AC XY: 305391 AN XY: 726680

Gnomad4 AFR exome AF: 0.843

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.334

Gnomad4 EAS exome AF: 0.970

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.547 AC: 83150 AN: 152036 Hom.: 26232 Cov.: 33 AF XY: 0.555 AC XY: 41213 AN XY: 74314

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.482

Alfa AF: 0.402 Hom.: 21222

Bravo AF: 0.566

TwinsUK AF: 0.364 AC: 1348

ALSPAC AF: 0.353 AC: 1360

ESP6500AA AF: 0.806 AC: 3390

ESP6500EA AF: 0.367 AC: 3087

ExAC AF: 0.521 AC: 62946

Asia WGS AF: 0.764 AC: 2654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.057
DANN	Benign	0.24
DEOGEN2	Benign	0.025	T;T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.12	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.48	.;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.023
Sift	Benign	1.0	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.017
MPC		0.13
ClinPred		0.024	T
GERP RS		-9.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.037
gMVP		0.11

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; COSMIC: COSV53473442; COSMIC: COSV53473442;