chr19-57769852-G-C

Variant names:

• chr19-57769852-G-C
• rs188488087
• NM_017652.4:c.10G>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.10G>C​(p.Ala4Pro) 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. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF586 NM_017652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.845
• Publications: 1 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=0.074801296).

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.10G>C	p.Ala4Pro	missense	Exon 1 of 3	NP_060122.2	Q9NXT0-1
	ZNF586	NM_001077426.3		c.10G>C	p.Ala4Pro	missense	Exon 1 of 2	NP_001070894.1	Q9NXT0-2
	ZNF586	NM_001204814.2		c.-170G>C		5_prime_UTR	Exon 1 of 4	NP_001191743.1	Q9NXT0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF586	ENST00000396154.7	TSL:1 MANE Select	c.10G>C	p.Ala4Pro	missense	Exon 1 of 3	ENSP00000379458.1	Q9NXT0-1
	ZNF586	ENST00000396150.4	TSL:1	c.10G>C	p.Ala4Pro	missense	Exon 1 of 2	ENSP00000379454.3	Q9NXT0-2
	ZNF586	ENST00000598885.5	TSL:4	c.10G>C	p.Ala4Pro	missense	Exon 1 of 3	ENSP00000470397.1	M0QZ99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000746 AC: 1 AN: 134024 AF XY: 0.00

Gnomad AFR exome AF: 0.000165

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1391056 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 686352

African (AFR) AF: 0.00 AC: 0 AN: 31366

American (AMR) AF: 0.00 AC: 0 AN: 35528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25058

East Asian (EAS) AF: 0.00 AC: 0 AN: 35186

South Asian (SAS) AF: 0.00 AC: 0 AN: 79144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077480

Other (OTH) AF: 0.00 AC: 0 AN: 57836

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.84
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.063
Sift	Benign	0.053	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.077	B
Vest4		0.31
MVP		0.11
MPC		0.097
ClinPred		0.072	T
GERP RS		-1.7
PromoterAI		-0.072	Neutral
Varity_R		0.21
gMVP		0.22
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: rs188488087; hg19: chr19-58281220;