chr10-56358869-T-C

Variant names:

• chr10-56358869-T-C
• rs2241666
• NM_007057.4:c.559A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (35932 hom., cov: 32)
  • Exomes 𝑓: 0.64 (306895 hom.)
• Consequence: ZWINT NM_007057.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZWINT	NM_007057.4	MANE Select	c.559A>G	p.Arg187Gly	missense	Exon 6 of 9	NP_008988.2
	ZWINT	NM_032997.3		c.559A>G	p.Arg187Gly	missense	Exon 6 of 8	NP_127490.1
	ZWINT	NM_001005413.1		c.519+40A>G		intron	N/A	NP_001005413.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZWINT	ENST00000373944.8	TSL:1 MANE Select	c.559A>G	p.Arg187Gly	missense	Exon 6 of 9	ENSP00000363055.3
	ZWINT	ENST00000318387.7	TSL:1	c.559A>G	p.Arg187Gly	missense	Exon 6 of 8	ENSP00000322850.3
	ZWINT	ENST00000920699.1		c.592A>G	p.Arg198Gly	missense	Exon 6 of 9	ENSP00000590758.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103793 AN: 151890 Hom.: 35898 Cov.: 32

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

GnomAD2 exomes AF: 0.684 AC: 171659 AN: 251110 AF XY: 0.680

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 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.: 74 AF XY: 0.646 AC XY: 470068 AN XY: 727222

African (AFR) AF: 0.757 AC: 25350 AN: 33480

American (AMR) AF: 0.793 AC: 35485 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 17510 AN: 26136

East Asian (EAS) AF: 0.846 AC: 33577 AN: 39700

South Asian (SAS) AF: 0.748 AC: 64510 AN: 86254

European-Finnish (FIN) AF: 0.576 AC: 30767 AN: 53392

Middle Eastern (MID) AF: 0.684 AC: 3948 AN: 5768

European-Non Finnish (NFE) AF: 0.622 AC: 691134 AN: 1112002

Other (OTH) AF: 0.658 AC: 39766 AN: 60394

GnomAD4 genome AF: 0.683 AC: 103879 AN: 152008 Hom.: 35932 Cov.: 32 AF XY: 0.685 AC XY: 50874 AN XY: 74294

African (AFR) AF: 0.761 AC: 31548 AN: 41456

American (AMR) AF: 0.757 AC: 11571 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4272 AN: 5146

South Asian (SAS) AF: 0.763 AC: 3678 AN: 4818

European-Finnish (FIN) AF: 0.589 AC: 6232 AN: 10572

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42101 AN: 67950

Other (OTH) AF: 0.688 AC: 1454 AN: 2112

Alfa AF: 0.645 Hom.: 56390

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.3
DANN	Benign	0.31
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	8.9e-7	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.28	N
PhyloP100		0.16
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.032
Sift	Benign	0.57	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.063
ClinPred		0.0096	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.017
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241666; hg19: chr10-58118630; COSMIC: COSV59185255;