19-57779087-A-T

Position:

• chr19-57779087-A-T

Variant summary

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

The NM_017652.4(ZNF586):​c.500A>T​(p.Gln167Leu) 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. 14/21 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: ZNF586 NM_017652.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.70

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=0.13527721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF586	NM_017652.4	c.500A>T	p.Gln167Leu	missense_variant	3/3	ENST00000396154.7	NP_060122.2
ZNF586	NM_001204814.2	c.371A>T	p.Gln124Leu	missense_variant	4/4		NP_001191743.1
ZNF586	NM_001077426.3	c.373A>T	p.Ser125Cys	missense_variant	2/2		NP_001070894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF586	ENST00000396154.7	c.500A>T	p.Gln167Leu	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

Nov 01, 2022

The c.500A>T (p.Q167L) alteration is located in exon 3 (coding exon 3) of the ZNF586 gene. This alteration results from a A to T substitution at nucleotide position 500, causing the glutamine (Q) at amino acid position 167 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.4
DANN	Benign	0.69
DEOGEN2	Benign	0.032	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.00069	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.9	D;N
REVEL	Benign	0.047
Sift	Benign	0.089	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.10	.;B
Vest4		0.17
MutPred		0.38		.;Loss of disorder (P = 0.1133);
MVP		0.048
MPC		0.078
ClinPred		0.089	T
GERP RS		0.30
Varity_R		0.068
gMVP		0.16

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: chr19-58290455;