chr18-58919174-A-C

Position:

• chr18-58919174-A-C

Variant summary

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

The NM_001375912.1(ZNF532):​c.887A>C​(p.Glu296Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)
• Consequence: ZNF532 NM_001375912.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

Genes affected

ZNF532 (HGNC:30940): (zinc finger protein 532) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [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=0.08443332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF532	NM_001375912.1	c.887A>C	p.Glu296Ala	missense_variant	3/10	ENST00000591808.6	NP_001362841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF532	ENST00000591808.6	c.887A>C	p.Glu296Ala	missense_variant	3/10	1	NM_001375912.1	ENSP00000468238.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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 30, 2022

The c.887A>C (p.E296A) alteration is located in exon 4 (coding exon 1) of the ZNF532 gene. This alteration results from a A to C substitution at nucleotide position 887, causing the glutamic acid (E) at amino acid position 296 to be replaced by an alanine (A). 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
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;T;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	.;.;.;.;D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.084	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M;M;M;M
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N;.;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.038	D;.;.;.;.
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.0	B;B;B;B;B
Vest4		0.19
MutPred		0.12		Gain of methylation at R295 (P = 0.0458);Gain of methylation at R295 (P = 0.0458);Gain of methylation at R295 (P = 0.0458);Gain of methylation at R295 (P = 0.0458);Gain of methylation at R295 (P = 0.0458);
MVP		0.068
MPC		0.59
ClinPred		0.30	T
GERP RS		3.8
Varity_R		0.11
gMVP		0.053

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: chr18-56586406;