19-15423101-T-C

Variant names:

• chr19-15423101-T-C
• rs1166436146
• NM_001371589.1:c.5645A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371589.1(WIZ):​c.5645A>G​(p.Gln1882Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: WIZ NM_001371589.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.73
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3040349).

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.5645A>G	p.Gln1882Arg	missense	Exon 13 of 13	NP_001358518.1	A0A669KAV7
	WIZ	NM_001439242.1		c.5246A>G	p.Gln1749Arg	missense	Exon 12 of 12	NP_001426171.1
	WIZ	NM_001411129.1		c.5075A>G	p.Gln1692Arg	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.5645A>G	p.Gln1882Arg	missense	Exon 13 of 13	ENSP00000500993.1	A0A669KAV7
	WIZ	ENST00000545156.5	TSL:1	c.2873A>G	p.Gln958Arg	missense	Exon 8 of 8	ENSP00000445824.1	O95785-3
	WIZ	ENST00000389282.8	TSL:1	c.2474A>G	p.Gln825Arg	missense	Exon 7 of 7	ENSP00000373933.5	B9EGQ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248514 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459844 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726268

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4502

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111732

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 32

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	0.088
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
PhyloP100		2.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.047	D
Polyphen		0.94	P
Vest4		0.26
MVP		0.22
MPC		0.48
ClinPred		0.98	D
GERP RS		5.1
gMVP		0.099
Mutation Taster		=87/13	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: rs1166436146; hg19: chr19-15533912;