chr19-15424739-C-T

Variant names:

• chr19-15424739-C-T
• rs776151852
• NM_001371589.1:c.5188G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001371589.1(WIZ):​c.5188G>A​(p.Gly1730Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,569,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: WIZ NM_001371589.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.561
• Publications: 0 publications found

Genes affected

WIZ (HGNC:30917): (WIZ zinc finger) Enables several functions, including DNA-binding transcription factor activity, RNA polymerase II-specific; histone methyltransferase binding activity; and transcription corepressor binding activity. Involved in positive regulation of nuclear cell cycle DNA replication and protein stabilization. Located in midbody and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046625644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371589.1. 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
	WIZ	NM_001371589.1	MANE Select	c.5188G>A	p.Gly1730Ser	missense	Exon 11 of 13	NP_001358518.1	A0A669KAV7
	WIZ	NM_001439242.1		c.4789G>A	p.Gly1597Ser	missense	Exon 10 of 12	NP_001426171.1
	WIZ	NM_001411129.1		c.4618G>A	p.Gly1540Ser	missense	Exon 9 of 11	NP_001398058.1	A0A2R8YFV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIZ	ENST00000673675.1	MANE Select	c.5188G>A	p.Gly1730Ser	missense	Exon 11 of 13	ENSP00000500993.1	A0A669KAV7
	WIZ	ENST00000545156.5	TSL:1	c.2416G>A	p.Gly806Ser	missense	Exon 6 of 8	ENSP00000445824.1	O95785-3
	WIZ	ENST00000389282.8	TSL:1	c.2017G>A	p.Gly673Ser	missense	Exon 5 of 7	ENSP00000373933.5	B9EGQ5

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000337 AC: 6 AN: 178226 AF XY: 0.0000405

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000141

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000219 AC: 31 AN: 1416858 Hom.: 0 Cov.: 33 AF XY: 0.0000228 AC XY: 16 AN XY: 701862

African (AFR) AF: 0.00 AC: 0 AN: 32522

American (AMR) AF: 0.000273 AC: 11 AN: 40338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24848

East Asian (EAS) AF: 0.00 AC: 0 AN: 37926

South Asian (SAS) AF: 0.00 AC: 0 AN: 81782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4756

European-Non Finnish (NFE) AF: 0.0000165 AC: 18 AN: 1093782

Other (OTH) AF: 0.0000341 AC: 2 AN: 58616

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74478

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000261 AC: 3

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	Benign	0.071
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.56
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.041
Sift	Benign	0.42	T
Sift4G	Benign	1.0	T
Polyphen		0.22	B
Vest4		0.16
MVP		0.043
MPC		0.53
ClinPred		0.030	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.37
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs776151852; hg19: chr19-15535550;