19-15424667-C-T

Variant names:

• chr19-15424667-C-T
• NM_001371589.1:c.5260G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001371589.1(WIZ):​c.5260G>A​(p.Ala1754Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WIZ NM_001371589.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.168

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059819162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIZ	NM_001371589.1	c.5260G>A	p.Ala1754Thr	missense_variant	Exon 11 of 13	ENST00000673675.1	NP_001358518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIZ	ENST00000673675.1	c.5260G>A	p.Ala1754Thr	missense_variant	Exon 11 of 13		NM_001371589.1	ENSP00000500993.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438258 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 715238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1975G>A (p.A659T) alteration is located in exon 6 (coding exon 5) of the WIZ gene. This alteration results from a G to A substitution at nucleotide position 1975, causing the alanine (A) at amino acid position 659 to be replaced by a threonine (T). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	.;T;.;T;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.79	T;T;T;T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.060	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.25	N;.;N;.;.;.
REVEL	Benign	0.058
Sift	Benign	0.49	T;.;T;.;.;.
Sift4G	Benign	0.49	T;T;T;T;T;.
Polyphen		0.048	B;.;.;.;.;.
Vest4		0.14
MVP		0.043
MPC		0.44
ClinPred		0.071	T
GERP RS		3.4
gMVP		0.21

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: chr19-15535478; COSMIC: COSV54605028;