Variant chr15-66528879-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000307897.10(ZWILCH):c.997G>T(p.Asp333Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZWILCH
ENST00000307897.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

ZWILCH (HGNC:25468): (zwilch kinetochore protein) Involved in protein localization to kinetochore. Located in kinetochore. Part of RZZ complex. [provided by Alliance of Genome Resources, Apr 2022]

ZWILCH links:

ZWILCH (HGNC:):

ZWILCH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ZWILCH	NM_017975.5 linkuse as main transcript	c.997G>T	p.Asp333Tyr	missense_variant	11/19	ENST00000307897.10	NP_060445.3	Q9H900-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZWILCH	ENST00000307897.10 linkuse as main transcript	c.997G>T	p.Asp333Tyr	missense_variant	11/19	1	NM_017975.5	ENSP00000311429.5		Q9H900-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000199

AC:

AN:

251318

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000289

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:

0.0000164

AC:

AN:

1461694

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000171

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.000131

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:

0.000196

ExAC

AF:

0.0000247

AC:

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

Jan 06, 2023

The c.997G>T (p.D333Y) alteration is located in exon 11 (coding exon 11) of the ZWILCH gene. This alteration results from a G to T substitution at nucleotide position 997, causing the aspartic acid (D) at amino acid position 333 to be replaced by a tyrosine (Y). 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

.;T;.;.;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.87

.;D;D;.;.

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.63

D;D;D;D;D

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.4

.;M;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.3

D;D;.;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.015

D;D;.;D;D

Sift4G

Benign

0.082

T;T;T;T;T

Polyphen

1.0

.;D;.;.;.

Vest4

0.64

MVP

0.64

MPC

0.22

ClinPred

0.84

GERP RS

5.4

Varity_R

0.29

gMVP

0.50

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