NM_017652.4:c.133C>A

Variant names:

• chr19-57776639-C-A
• NM_017652.4:c.133C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017652.4(ZNF586):​c.133C>A​(p.Leu45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF586 NM_017652.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.351
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017652.4. 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
	ZNF586	NM_017652.4	MANE Select	c.133C>A	p.Leu45Met	missense	Exon 2 of 3	NP_060122.2	Q9NXT0-1
	ZNF586	NM_001204814.2		c.4C>A	p.Leu2Met	missense	Exon 3 of 4	NP_001191743.1	Q9NXT0-3
	ZNF586	NM_001077426.3		c.37-2112C>A		intron	N/A	NP_001070894.1	Q9NXT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF586	ENST00000396154.7	TSL:1 MANE Select	c.133C>A	p.Leu45Met	missense	Exon 2 of 3	ENSP00000379458.1	Q9NXT0-1
	ZNF586	ENST00000396150.4	TSL:1	c.37-2112C>A		intron	N/A	ENSP00000379454.3	Q9NXT0-2
	ZNF586	ENST00000391702.3	TSL:2	c.4C>A	p.Leu2Met	missense	Exon 3 of 4	ENSP00000375583.3	Q9NXT0-3

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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0022	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.35
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.33
MutPred		0.78		Gain of helix (P = 0.132)
MVP		0.088
MPC		0.39
ClinPred		0.72	D
GERP RS		0.70
Varity_R		0.49
gMVP		0.046
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr19-58288007;