chr19-57779164-C-G

Position:

• chr19-57779164-C-G

Variant summary

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

The NM_017652.4(ZNF586):​c.577C>G​(p.Leu193Val) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF586 NM_017652.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0920

Genes affected

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

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=0.22069845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF586	NM_017652.4	c.577C>G	p.Leu193Val	missense_variant	3/3	ENST00000396154.7	NP_060122.2
ZNF586	NM_001204814.2	c.448C>G	p.Leu150Val	missense_variant	4/4		NP_001191743.1
ZNF586	NM_001077426.3	c.450C>G	p.Val150Val	synonymous_variant	2/2		NP_001070894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF586	ENST00000396154.7	c.577C>G	p.Leu193Val	missense_variant	3/3	1	NM_017652.4	ENSP00000379458.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Aug 27, 2024

The c.577C>G (p.L193V) alteration is located in exon 3 (coding exon 3) of the ZNF586 gene. This alteration results from a C to G substitution at nucleotide position 577, causing the leucine (L) at amino acid position 193 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.019	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	.;D
Vest4		0.19
MutPred		0.61		.;Gain of methylation at K190 (P = 0.0611);
MVP		0.20
MPC		0.40
ClinPred		0.81	D
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.098
gMVP		0.26

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: chr19-58290532;