NM_024762.3:c.282G>C

Variant names:

• chr19-57808982-C-G
• rs1987804064
• NM_024762.3:c.282G>C

Variant summary

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

The NM_024762.3(ZNF552):​c.282G>C​(p.Glu94Asp) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF552 NM_024762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.967
• Publications: 0 publications found

Genes affected

ZNF552 (HGNC:26135): (zinc finger protein 552) 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]

ZNF586 (HGNC:25949): (zinc finger protein 586) 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=0.060080856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024762.3. 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
	ZNF552	NM_024762.3	MANE Select	c.282G>C	p.Glu94Asp	missense	Exon 3 of 3	NP_079038.2	Q9H707

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF552	ENST00000391701.1	TSL:2 MANE Select	c.282G>C	p.Glu94Asp	missense	Exon 3 of 3	ENSP00000375582.1	Q9H707
	ZNF586	ENST00000598885.5	TSL:4	c.164-5444C>G		intron	N/A	ENSP00000470397.1	M0QZ99
	ZNF552	ENST00000594473.1	TSL:2	c.109+4312G>C		intron	N/A	ENSP00000472459.1	M0R2C3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.43
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.94	L
PhyloP100		-0.97
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.019
Sift	Benign	0.17	T
Sift4G	Benign	0.31	T
Polyphen		0.092	B
Vest4		0.070
MutPred		0.33		Loss of ubiquitination at K89 (P = 0.1191)
MVP		0.24
MPC		1.4
ClinPred		0.35	T
GERP RS		-0.33
Varity_R		0.081
gMVP		0.029
Mutation Taster		=91/9	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: rs1987804064; hg19: chr19-58320350;