19-57779087-A-C

Variant names:

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

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>C​(p.Gln167Pro) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q167L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF586 NM_017652.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.18431136).

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>C	p.Gln167Pro	missense	Exon 3 of 3	NP_060122.2	Q9NXT0-1
	ZNF586	NM_001204814.2		c.371A>C	p.Gln124Pro	missense	Exon 4 of 4	NP_001191743.1	Q9NXT0-3
	ZNF586	NM_001077426.3		c.373A>C	p.Ser125Arg	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>C	p.Gln167Pro	missense	Exon 3 of 3	ENSP00000379458.1	Q9NXT0-1
	ZNF586	ENST00000396150.4	TSL:1	c.373A>C	p.Ser125Arg	missense	Exon 2 of 2	ENSP00000379454.3	Q9NXT0-2
	ZNF586	ENST00000391702.3	TSL:2	c.371A>C	p.Gln124Pro	missense	Exon 4 of 4	ENSP00000375583.3	Q9NXT0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-2.7
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.12
Sift	Benign	0.037	D
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.29
MutPred		0.29		Gain of glycosylation at Q167 (P = 0.0388)
MVP		0.048
MPC		0.096
ClinPred		0.38	T
GERP RS		0.30
Varity_R		0.20
gMVP		0.43
Mutation Taster		=96/4	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;