chr19-57779087-A-T

Variant names:

• chr19-57779087-A-T
• rs1600081472
• NM_017652.4:c.500A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13527721).

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.500A>T	p.Gln167Leu	missense	Exon 3 of 3	NP_060122.2	Q9NXT0-1
	ZNF586	NM_001204814.2		c.371A>T	p.Gln124Leu	missense	Exon 4 of 4	NP_001191743.1	Q9NXT0-3
	ZNF586	NM_001077426.3		c.373A>T	p.Ser125Cys	missense	Exon 2 of 2	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.500A>T	p.Gln167Leu	missense	Exon 3 of 3	ENSP00000379458.1	Q9NXT0-1
	ZNF586	ENST00000396150.4	TSL:1	c.373A>T	p.Ser125Cys	missense	Exon 2 of 2	ENSP00000379454.3	Q9NXT0-2
	ZNF586	ENST00000391702.3	TSL:2	c.371A>T	p.Gln124Leu	missense	Exon 4 of 4	ENSP00000375583.3	Q9NXT0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.17
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
M_CAP	Benign	0.00069	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		-2.7
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.047
Sift	Benign	0.089	T
Sift4G	Benign	0.41	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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1600081472; hg19: chr19-58290455;