Genetic Variant NM_017706.5:c.92C>T (chr5-140665004-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017706.5(WDR55):c.92C>T(p.Thr31Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WDR55
NM_017706.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Variant links:

Genes affected

WDR55 (HGNC:25971): (WD repeat domain 55) Predicted to be involved in rRNA processing. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

WDR55 links:

LOC124901088 (HGNC:):

LOC124901088 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.34486696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR55	NM_017706.5 link	c.92C>T	p.Thr31Ile	missense_variant	Exon 1 of 7	ENST00000358337.10	NP_060176.3	Q9H6Y2-1
WDR55	XM_005268469.4 link	c.92C>T	p.Thr31Ile	missense_variant	Exon 1 of 8		XP_005268526.1	Q9H6Y2-1
WDR55	XM_017009600.3 link	c.-462C>T		5_prime_UTR_variant	Exon 1 of 8		XP_016865089.1	G3V1J0
LOC124901088	XR_007058968.1 link	n.227G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR55	ENST00000358337.10 link	c.92C>T	p.Thr31Ile	missense_variant	Exon 1 of 7	1	NM_017706.5	ENSP00000351100.5		Q9H6Y2-1
WDR55	ENST00000506393.5 link	n.92C>T		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000426304.1		D6RGJ8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249498

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461648

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.92C>T (p.T31I) alteration is located in exon 1 (coding exon 1) of the WDR55 gene. This alteration results from a C to T substitution at nucleotide position 92, causing the threonine (T) at amino acid position 31 to be replaced by an isoleucine (I). 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

0.30

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Benign

0.11

Sift4G

Uncertain

0.043

Polyphen

0.99

Vest4

0.61

MutPred

0.14

Loss of phosphorylation at T31 (P = 0.0144);

MVP

0.49

MPC

0.29

ClinPred

0.93

GERP RS

5.2

Varity_R

0.25

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over