19-36449651-T-A

Position:

• chr19-36449651-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145344.1(ZNF566):​c.583A>T​(p.Ile195Phe) 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: ZNF566 NM_001145344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0730

Genes affected

ZNF566 (HGNC:25919): (zinc finger protein 566) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07600278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF566	NM_001145344.1	c.583A>T	p.Ile195Phe	missense_variant	5/5	ENST00000452939.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF566	ENST00000452939.7	c.583A>T	p.Ile195Phe	missense_variant	5/5	2	NM_001145344.1	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 07, 2022

The c.586A>T (p.I196F) alteration is located in exon 5 (coding exon 4) of the ZNF566 gene. This alteration results from a A to T substitution at nucleotide position 586, causing the isoleucine (I) at amino acid position 196 to be replaced by a phenylalanine (F). 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	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.8
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T;T;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.73	T;T;T;.;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.076	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.94	L;.;.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.060	N;.;N;N;N
REVEL	Benign	0.028
Sift	Uncertain	0.0090	D;.;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D;.
Polyphen		0.0010	B;.;.;B;.
Vest4		0.053
MutPred		0.37		Gain of helix (P = 0.062);.;.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.17
ClinPred		0.15	T
GERP RS		-3.3
Varity_R		0.057
gMVP		0.064

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36940553;