dbSNP rs145387404: ZWINT:p.Arg177Leu (chr10-56358898-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007057.4(ZWINT):c.530G>T(p.Arg177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R177H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZWINT
NM_007057.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15593106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZWINT	NM_007057.4 link	c.530G>T	p.Arg177Leu	missense_variant	Exon 6 of 9	ENST00000373944.8	NP_008988.2	O95229-1
ZWINT	NM_032997.3 link	c.530G>T	p.Arg177Leu	missense_variant	Exon 6 of 8		NP_127490.1	O95229-1
ZWINT	NM_001005413.1 link	c.519+11G>T		intron_variant	Intron 6 of 8		NP_001005413.1	O95229-2
ZWINT	XR_428692.4 link	n.567G>T		non_coding_transcript_exon_variant	Exon 6 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZWINT	ENST00000373944.8 link	c.530G>T	p.Arg177Leu	missense_variant	Exon 6 of 9	1	NM_007057.4	ENSP00000363055.3		O95229-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.67

.;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.6

L;L;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.066

T;T;T

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.24

MutPred

0.34

Loss of ubiquitination at K178 (P = 0.0561);Loss of ubiquitination at K178 (P = 0.0561);.;

MVP

0.30

MPC

0.11

ClinPred

0.76

GERP RS

1.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.38

gMVP

0.10

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over