Variant 10-56358869-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007057.4(ZWINT):c.559A>G(p.Arg187Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,613,858 control chromosomes in the GnomAD database, including 342,827 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.68 ( 35932 hom., cov: 32)

Exomes 𝑓: 0.64 ( 306895 hom. )

Consequence

ZWINT
NM_007057.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.159

Variant links:

Genes affected

ZWINT (HGNC:13195): (ZW10 interacting kinetochore protein) This gene encodes a protein that is clearly involved in kinetochore function although an exact role is not known. It interacts with ZW10, another kinetochore protein, possibly regulating the association between ZW10 and kinetochores. The encoded protein localizes to prophase kinetochores before ZW10 does and it remains detectable on the kinetochore until late anaphase. It has a uniform distribution in the cytoplasm of interphase cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ZWINT links:

ZWINT (HGNC:):

ZWINT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.852489E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZWINT	NM_007057.4 linkuse as main transcript	c.559A>G	p.Arg187Gly	missense_variant	6/9	ENST00000373944.8	NP_008988.2	O95229-1
ZWINT	NM_032997.3 linkuse as main transcript	c.559A>G	p.Arg187Gly	missense_variant	6/8		NP_127490.1	O95229-1
ZWINT	NM_001005413.1 linkuse as main transcript	c.519+40A>G		intron_variant			NP_001005413.1	O95229-2
ZWINT	XR_428692.4 linkuse as main transcript	n.596A>G		non_coding_transcript_exon_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZWINT	ENST00000373944.8 linkuse as main transcript	c.559A>G	p.Arg187Gly	missense_variant	6/9	1	NM_007057.4	ENSP00000363055.3		O95229-1

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103793

AN:

151890

Hom.:

35898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.761

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.757

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.830

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.726

Gnomad NFE

AF:

0.620

Gnomad OTH

AF:

0.685

GnomAD3 exomes

AF:

0.684

AC:

171659

AN:

251110

Hom.:

59728

AF XY:

0.680

AC XY:

92349

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.766

Gnomad AMR exome

AF:

0.800

Gnomad ASJ exome

AF:

0.671

Gnomad EAS exome

AF:

0.819

Gnomad SAS exome

AF:

0.746

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.680

GnomAD4 exome

AF:

0.644

AC:

942047

AN:

1461850

Hom.:

306895

Cov.:

AF XY:

0.646

AC XY:

470068

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.757

Gnomad4 AMR exome

AF:

0.793

Gnomad4 ASJ exome

AF:

0.670

Gnomad4 EAS exome

AF:

0.846

Gnomad4 SAS exome

AF:

0.748

Gnomad4 FIN exome

AF:

0.576

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.658

GnomAD4 genome

AF:

0.683

AC:

103879

AN:

152008

Hom.:

35932

Cov.:

AF XY:

0.685

AC XY:

50874

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.761

Gnomad4 AMR

AF:

0.757

Gnomad4 ASJ

AF:

0.676

Gnomad4 EAS

AF:

0.830

Gnomad4 SAS

AF:

0.763

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.620

Gnomad4 OTH

AF:

0.688

Alfa

AF:

0.637

Hom.:

41205

Bravo

AF:

0.695

TwinsUK

AF:

0.628

AC:

2327

ALSPAC

AF:

0.626

AC:

2413

ESP6500AA

AF:

0.753

AC:

3318

ESP6500EA

AF:

0.631

AC:

5429

ExAC

AF:

0.680

AC:

82586

Asia WGS

AF:

0.792

AC:

2752

AN:

3478

EpiCase

AF:

0.625

EpiControl

AF:

0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.3

DANN

Benign

0.31

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.31

.;T;T

MetaRNN

Benign

8.9e-7

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.28

N;N;.

PrimateAI

Benign

0.18

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.032

Sift

Benign

0.57

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.021

MPC

0.063

ClinPred

0.0096

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.093

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over