3-196554236-G-A

Position:

• chr3-196554236-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182627.3(WDR53):​c.1052C>T​(p.Ser351Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR53 NM_182627.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11

Genes affected

WDR53 (HGNC:28786): (WD repeat domain 53) This gene encodes a protein containing WD domains. The function of this gene is unknown. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR53	NM_182627.3	c.1052C>T	p.Ser351Phe	missense_variant	4/4	ENST00000332629.7	NP_872433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR53	ENST00000332629.7	c.1052C>T	p.Ser351Phe	missense_variant	4/4	1	NM_182627.3	ENSP00000328079.5
WDR53	ENST00000433160.1	c.575C>T	p.Ser192Phe	missense_variant	3/3	5		ENSP00000410677.1
WDR53	ENST00000429115.1	c.569C>T	p.Ser190Phe	missense_variant	2/2	2		ENSP00000396668.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 02, 2024

The c.1052C>T (p.S351F) alteration is located in exon 4 (coding exon 2) of the WDR53 gene. This alteration results from a C to T substitution at nucleotide position 1052, causing the serine (S) at amino acid position 351 to be replaced by a phenylalanine (F). 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	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	-0.098	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.54
MutPred		0.52		Loss of disorder (P = 0.0095);.;.;
MVP		0.90
MPC		0.73
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.54
gMVP		0.78

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: chr3-196281107;