chr11-113739234-C-A

Variant names:

• chr11-113739234-C-A
• rs146035001
• NM_004724.4:c.1732G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004724.4(ZW10):​c.1732G>T​(p.Val578Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: ZW10 NM_004724.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 2 publications found

Genes affected

ZW10 (HGNC:13194): (zw10 kinetochore protein) This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. This protein is an essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZW10	NM_004724.4	MANE Select	c.1732G>T	p.Val578Leu	missense	Exon 12 of 16	NP_004715.1	O43264-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZW10	ENST00000200135.8	TSL:1 MANE Select	c.1732G>T	p.Val578Leu	missense	Exon 12 of 16	ENSP00000200135.3	O43264-1
	ZW10	ENST00000898961.1		c.1738G>T	p.Val580Leu	missense	Exon 12 of 16	ENSP00000569020.1
	ZW10	ENST00000936157.1		c.1726G>T	p.Val576Leu	missense	Exon 12 of 16	ENSP00000606216.1

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.000397

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000119 AC: 30 AN: 251090 AF XY: 0.000111

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000871

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000372 AC: 544 AN: 1461602 Hom.: 0 Cov.: 31 AF XY: 0.000364 AC XY: 265 AN XY: 727092

African (AFR) AF: 0.0000598 AC: 2 AN: 33464

American (AMR) AF: 0.0000895 AC: 4 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000466 AC: 518 AN: 1111896

Other (OTH) AF: 0.000315 AC: 19 AN: 60390

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74328

African (AFR) AF: 0.0000724 AC: 3 AN: 41440

American (AMR) AF: 0.000262 AC: 4 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.000212

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.021	D
Polyphen		0.55	P
Vest4		0.88
MutPred		0.79		Gain of helix (P = 0.132)
MVP		0.48
MPC		0.50
ClinPred		0.18	T
GERP RS		5.0
Varity_R		0.42
gMVP		0.69
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs146035001; hg19: chr11-113609956;