19-15424741-A-C

Position:

• chr19-15424741-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371589.1(WIZ):​c.5186T>G​(p.Val1729Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict 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: 2.50

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1876095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIZ	NM_001371589.1	c.5186T>G	p.Val1729Gly	missense_variant	11/13	ENST00000673675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIZ	ENST00000673675.1	c.5186T>G	p.Val1729Gly	missense_variant	11/13		NM_001371589.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2021

The c.1901T>G (p.V634G) alteration is located in exon 6 (coding exon 5) of the WIZ gene. This alteration results from a T to G substitution at nucleotide position 1901, causing the valine (V) at amino acid position 634 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	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	.;T;.;T;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.73	T;T;T;T;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.6	N;.;N;.;.;.
REVEL	Benign	0.075
Sift	Uncertain	0.0010	D;.;D;.;.;.
Sift4G	Benign	0.39	T;T;T;T;T;.
Polyphen		0.96	D;.;.;.;.;.
Vest4		0.32
MVP		0.043
MPC		1.3
ClinPred		0.43	T
GERP RS		4.5
gMVP		0.55

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: chr19-15535552;