19-57814715-A-C

Position:

• chr19-57814715-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024762.3(ZNF552):​c.29T>G​(p.Val10Gly) 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. 15/21 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: ZNF552 NM_024762.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0630

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]

ZNF552 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06333712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF552	NM_024762.3	c.29T>G	p.Val10Gly	missense_variant	1/3	ENST00000391701.1	NP_079038.2
ZNF552	XM_005259267.5	c.-162T>G		5_prime_UTR_variant	1/3		XP_005259324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF552	ENST00000391701.1	c.29T>G	p.Val10Gly	missense_variant	1/3	2	NM_024762.3	ENSP00000375582.1
ZNF586	ENST00000599802.1	c.37-4853A>C		intron_variant		3		ENSP00000472972.1
ZNF552	ENST00000596248.1	n.29T>G		non_coding_transcript_exon_variant	1/3	2		ENSP00000470362.1
ZNF552	ENST00000600397.1	n.199T>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Dec 02, 2022

The c.29T>G (p.V10G) alteration is located in exon 1 (coding exon 1) of the ZNF552 gene. This alteration results from a T to G substitution at nucleotide position 29, causing the valine (V) at amino acid position 10 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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.7
DANN	Benign	0.65
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.0010	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.011
Sift	Benign	0.080	T
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.37		Gain of disorder (P = 0.0345);
MVP		0.081
MPC		0.78
ClinPred		0.099	T
GERP RS		-0.77
Varity_R		0.065
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1987927584; hg19: chr19-58326083;