19-15423132-G-A

Variant names:

• chr19-15423132-G-A
• rs1290831770
• NM_001371589.1:c.5614C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/19 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. P1872A) 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
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14667463).

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.5614C>T	p.Pro1872Ser	missense	Exon 13 of 13	NP_001358518.1	A0A669KAV7
	WIZ	NM_001439242.1		c.5215C>T	p.Pro1739Ser	missense	Exon 12 of 12	NP_001426171.1
	WIZ	NM_001411129.1		c.5044C>T	p.Pro1682Ser	missense	Exon 11 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.5614C>T	p.Pro1872Ser	missense	Exon 13 of 13	ENSP00000500993.1	A0A669KAV7
	WIZ	ENST00000545156.5	TSL:1	c.2842C>T	p.Pro948Ser	missense	Exon 8 of 8	ENSP00000445824.1	O95785-3
	WIZ	ENST00000389282.8	TSL:1	c.2443C>T	p.Pro815Ser	missense	Exon 7 of 7	ENSP00000373933.5	B9EGQ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.072
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.060
Sift	Benign	0.031	D
Sift4G	Benign	0.21	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
Mutation Taster		=75/25	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: rs1290831770; hg19: chr19-15533943;