chr3-196554696-C-T

Position:

• chr3-196554696-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182627.3(WDR53):​c.592G>A​(p.Ala198Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: WDR53 NM_182627.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.34

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28984702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR53	NM_182627.3	c.592G>A	p.Ala198Thr	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.592G>A	p.Ala198Thr	missense_variant	4/4	1	NM_182627.3	ENSP00000328079.5
WDR53	ENST00000433160.1	c.115G>A	p.Ala39Thr	missense_variant	3/3	5		ENSP00000410677.1
WDR53	ENST00000429115.1	c.109G>A	p.Ala37Thr	missense_variant	2/2	2		ENSP00000396668.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

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

Dec 17, 2023

The c.592G>A (p.A198T) alteration is located in exon 4 (coding exon 2) of the WDR53 gene. This alteration results from a G to A substitution at nucleotide position 592, causing the alanine (A) at amino acid position 198 to be replaced by a threonine (T). 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	0.29
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.065
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.17	T;T;T
Polyphen		0.80	P;.;.
Vest4		0.21
MutPred		0.28		Gain of glycosylation at A198 (P = 0.0539);.;.;
MVP		0.40
MPC		0.30
ClinPred		0.79	D
GERP RS		4.0
Varity_R		0.17
gMVP		0.24

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: chr3-196281567;