Variant 15-66519031-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000307897.10(ZWILCH):c.473C>G(p.Thr158Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00057 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

ZWILCH
ENST00000307897.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.913

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:

RPL4 (HGNC:10353): (ribosomal protein L4) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L4E family of ribosomal proteins. It is located in the cytoplasm. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

RPL4 links:

ZWILCH (HGNC:):

ZWILCH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014142722).

BP6

Variant 15-66519031-C-G is Benign according to our data. Variant chr15-66519031-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645474.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZWILCH	NM_017975.5 linkuse as main transcript	c.473C>G	p.Thr158Arg	missense_variant	5/19	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.473C>G	p.Thr158Arg	missense_variant	5/19	1	NM_017975.5	ENSP00000311429.5		Q9H900-1

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000916

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:

0.000838

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000461

AC:

116

AN:

251480

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000826

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000569

AC:

832

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000705

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000578

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000853

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000580

Hom.:

Bravo

AF:

0.000578

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ZWILCH: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0038

.;T;.;.;.;T

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.68

.;T;T;.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

.;M;.;.;.;.

MutationTaster

Benign

0.73

N;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.89

N;N;.;N;N;D

REVEL

Benign

0.12

Sift

Uncertain

0.0090

D;D;.;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D;D

Polyphen

0.90

.;P;.;.;.;.

Vest4

0.26

MVP

0.45

MPC

0.15

ClinPred

0.072

GERP RS

4.7

Varity_R

0.15

gMVP

0.34

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