18-58918433-A-G

Variant names:

• chr18-58918433-A-G
• rs1414599181
• NM_001375912.1:c.146A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

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=0.18761408).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375912.1. 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
	ZNF532	NM_001375912.1	MANE Select	c.146A>G	p.Asp49Gly	missense	Exon 3 of 10	NP_001362841.1	Q9HCE3
	ZNF532	NM_001318726.2		c.146A>G	p.Asp49Gly	missense	Exon 3 of 10	NP_001305655.1	Q9HCE3
	ZNF532	NM_001318727.2		c.146A>G	p.Asp49Gly	missense	Exon 3 of 10	NP_001305656.1	Q9HCE3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF532	ENST00000591808.6	TSL:1 MANE Select	c.146A>G	p.Asp49Gly	missense	Exon 3 of 10	ENSP00000468238.1	Q9HCE3
	ZNF532	ENST00000336078.8	TSL:1	c.146A>G	p.Asp49Gly	missense	Exon 4 of 11	ENSP00000338217.4	Q9HCE3
	ZNF532	ENST00000591083.5	TSL:1	c.146A>G	p.Asp49Gly	missense	Exon 3 of 10	ENSP00000468532.1	Q9HCE3

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	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PhyloP100		8.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.12	T
Polyphen		0.072	B
Vest4		0.13
MutPred		0.21		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

Other links and lift over

dbSNP: rs1414599181; hg19: chr18-56585665;