Variant 2-189465203-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032168.3(WDR75):c.1238C>T(p.Thr413Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,612,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

WDR75
NM_032168.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

WDR75 (HGNC:25725): (WD repeat domain 75) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

WDR75 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046542466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR75	NM_032168.3 linkuse as main transcript	c.1238C>T	p.Thr413Ile	missense_variant	12/21	ENST00000314761.9	NP_115544.1
WDR75	NM_001303096.2 linkuse as main transcript	c.1046C>T	p.Thr349Ile	missense_variant	13/22		NP_001290025.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WDR75	ENST00000314761.9 linkuse as main transcript	c.1238C>T	p.Thr413Ile	missense_variant	12/21	1	NM_032168.3	ENSP00000314193	P1
WDR75	ENST00000427960.5 linkuse as main transcript	c.*2602C>T		3_prime_UTR_variant, NMD_transcript_variant	12/21	1		ENSP00000400728
WDR75	ENST00000436347.5 linkuse as main transcript	c.*1002C>T		3_prime_UTR_variant, NMD_transcript_variant	13/22	2		ENSP00000414226

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

250800

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135562

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000251

AC:

367

AN:

1460882

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

174

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000171

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.000155

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000274

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.1238C>T (p.T413I) alteration is located in exon 12 (coding exon 12) of the WDR75 gene. This alteration results from a C to T substitution at nucleotide position 1238, causing the threonine (T) at amino acid position 413 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.73

M_CAP

Benign

0.012

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

REVEL

Benign

0.071

Sift

Uncertain

0.015

Sift4G

Uncertain

0.055

Polyphen

0.059

Vest4

0.17

MVP

0.082

MPC

0.18

ClinPred

0.046

GERP RS

3.8

Varity_R

0.071

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

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