chr3-196554522-G-T

Position:

• chr3-196554522-G-T

Variant summary

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

The NM_182627.3(WDR53):​c.766C>A​(p.Leu256Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR53 NM_182627.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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.766C>A	p.Leu256Met	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.766C>A	p.Leu256Met	missense_variant	4/4	1	NM_182627.3	ENSP00000328079.5
WDR53	ENST00000433160.1	c.289C>A	p.Leu97Met	missense_variant	3/3	5		ENSP00000410677.1
WDR53	ENST00000429115.1	c.283C>A	p.Leu95Met	missense_variant	2/2	2		ENSP00000396668.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Feb 05, 2024

The c.766C>A (p.L256M) alteration is located in exon 4 (coding exon 2) of the WDR53 gene. This alteration results from a C to A substitution at nucleotide position 766, causing the leucine (L) at amino acid position 256 to be replaced by a methionine (M). 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	Benign	0.26
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.094	T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;D;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.031	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.38
MutPred		0.69		Loss of stability (P = 0.0039);.;.;
MVP		0.63
MPC		0.74
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.41

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: chr3-196281393;