19-15424258-A-C

Variant names:

• chr19-15424258-A-C
• NM_001371589.1:c.5435T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371589.1(WIZ):​c.5435T>G​(p.Val1812Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WIZ NM_001371589.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32827845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIZ	NM_001371589.1	c.5435T>G	p.Val1812Gly	missense_variant	Exon 12 of 13	ENST00000673675.1	NP_001358518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIZ	ENST00000673675.1	c.5435T>G	p.Val1812Gly	missense_variant	Exon 12 of 13		NM_001371589.1	ENSP00000500993.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2150T>G (p.V717G) alteration is located in exon 7 (coding exon 6) of the WIZ gene. This alteration results from a T to G substitution at nucleotide position 2150, causing the valine (V) at amino acid position 717 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	.;T;.;T;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.1	N;.;N;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.093	T;.;T;.;.;.
Sift4G	Uncertain	0.021	D;D;D;D;D;.
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.55
MVP		0.22
MPC		1.5
ClinPred		0.86	D
GERP RS		5.2
gMVP		0.67

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15535069;