chr18-58918708-G-T

Variant names:

• chr18-58918708-G-T
• rs1392295825
• NM_001375912.1:c.421G>T

Variant summary

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

The NM_001375912.1(ZNF532):​c.421G>T​(p.Asp141Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D141N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF532 NM_001375912.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32175598).

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.421G>T	p.Asp141Tyr	missense	Exon 3 of 10	NP_001362841.1	Q9HCE3
	ZNF532	NM_001318726.2		c.421G>T	p.Asp141Tyr	missense	Exon 3 of 10	NP_001305655.1	Q9HCE3
	ZNF532	NM_001318727.2		c.421G>T	p.Asp141Tyr	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.421G>T	p.Asp141Tyr	missense	Exon 3 of 10	ENSP00000468238.1	Q9HCE3
	ZNF532	ENST00000336078.8	TSL:1	c.421G>T	p.Asp141Tyr	missense	Exon 4 of 11	ENSP00000338217.4	Q9HCE3
	ZNF532	ENST00000591083.5	TSL:1	c.421G>T	p.Asp141Tyr	missense	Exon 3 of 10	ENSP00000468532.1	Q9HCE3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		8.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.31
Sift	Benign	0.26	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.70
MutPred		0.28		Gain of phosphorylation at D141 (P = 6e-04)
MVP		0.043
MPC		1.7
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.35
gMVP		0.17
Mutation Taster		=74/26	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: rs1392295825; hg19: chr18-56585940;