18-58918433-A-G

Position:

• chr18-58918433-A-G

Variant summary

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

The NM_001375912.1(ZNF532):​c.146A>G​(p.Asp49Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 8.88

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=0.18761408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF532	NM_001375912.1	c.146A>G	p.Asp49Gly	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.146A>G	p.Asp49Gly	missense_variant	3/10	1	NM_001375912.1	ENSP00000468238.1

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

May 01, 2024

The c.146A>G (p.D49G) alteration is located in exon 4 (coding exon 1) of the ZNF532 gene. This alteration results from a A to G substitution at nucleotide position 146, causing the aspartic acid (D) at amino acid position 49 to be replaced by a glycine (G). 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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;T;T;T;.;T;T;.;T;T;T;.;.;T;T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	.;.;D;D;D;.;.;D;D;D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;L;.;.;.;L;L;.;.;L;.;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T;D;T
Polyphen		0.072	B;B;.;.;.;B;B;.;.;B;.;.;.;.;.
Vest4		0.13
MutPred		0.21		Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);Loss of stability (P = 0.0257);.;
MVP		0.068
MPC		0.82
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.077

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: rs1414599181; hg19: chr18-56585665;