19-52406603-C-G

Variant names:

• chr19-52406603-C-G
• rs200968350
• NM_032423.3:c.231C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032423.3(ZNF528):​c.231C>G​(p.Asn77Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF528 NM_032423.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 0 publications found

Genes affected

ZNF528 (HGNC:29384): (zinc finger protein 528) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061533242).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032423.3. 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
	ZNF528	NM_032423.3	MANE Select	c.231C>G	p.Asn77Lys	missense	Exon 6 of 7	NP_115799.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF528	ENST00000360465.8	TSL:1 MANE Select	c.231C>G	p.Asn77Lys	missense	Exon 6 of 7	ENSP00000353652.3	Q3MIS6-1
	ZNF528	ENST00000862203.1		c.231C>G	p.Asn77Lys	missense	Exon 5 of 6	ENSP00000532262.1
	ZNF528	ENST00000862204.1		c.231C>G	p.Asn77Lys	missense	Exon 5 of 6	ENSP00000532263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.063
DANN	Benign	0.16
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.00076	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		-1.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.0090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.062
MutPred		0.41		Gain of ubiquitination at N77 (P = 0.0109)
MVP		0.21
MPC		0.0092
ClinPred		0.036	T
GERP RS		-2.2
Varity_R		0.040
gMVP		0.0093
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200968350; hg19: chr19-52909856;