chr19-15423132-G-A

Position:

• chr19-15423132-G-A

Variant summary

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

The NM_001371589.1(WIZ):​c.5614C>T​(p.Pro1872Ser) 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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1872L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WIZ NM_001371589.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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=0.14667463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIZ	NM_001371589.1	c.5614C>T	p.Pro1872Ser	missense_variant	13/13	ENST00000673675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIZ	ENST00000673675.1	c.5614C>T	p.Pro1872Ser	missense_variant	13/13		NM_001371589.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 06, 2023

The c.2329C>T (p.P777S) alteration is located in exon 8 (coding exon 7) of the WIZ gene. This alteration results from a C to T substitution at nucleotide position 2329, causing the proline (P) at amino acid position 777 to be replaced by a serine (S). 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	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	.;T;.;T;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.71	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;.;N;.;.;.
REVEL	Benign	0.060
Sift	Benign	0.031	D;.;D;.;.;.
Sift4G	Benign	0.21	T;T;T;T;T;.
Polyphen		0.069	B;.;.;.;.;.
Vest4		0.23
MVP		0.068
MPC		0.45
ClinPred		0.16	T
GERP RS		4.1
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1290831770; hg19: chr19-15533943;