ENST00000444991.6:c.1879C>G

Variant names:

• chr19-36997570-C-G
• rs1644698
• ENST00000444991.6:c.1879C>G
• ZNF568 p.Pro627Ala

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444991.6(ZNF568):​c.1879C>G​(p.Pro627Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,574,466 control chromosomes in the GnomAD database, including 222,477 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (22112 hom., cov: 31)
  • Exomes 𝑓: 0.53 (200365 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.58
• Publications: 13 publications found

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) 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 embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291239 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.547529E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444991.6. 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
	ZNF568	NM_001204838.2		c.1879C>G	p.Pro627Ala	missense	Exon 10 of 10	NP_001191767.1	C9JLX5
	ZNF568	NM_001204839.2		c.1687C>G	p.Pro563Ala	missense	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF568	ENST00000444991.6	TSL:1	c.1879C>G	p.Pro627Ala	missense	Exon 10 of 10	ENSP00000389794.2	C9JLX5
	ENSG00000291239	ENST00000706165.1		c.1879C>G	p.Pro627Ala	missense	Exon 12 of 12	ENSP00000516244.1	C9JLX5
	ZNF568	ENST00000591887.1	TSL:1	n.2048C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80890 AN: 151446 Hom.: 22078 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.535 AC: 108424 AN: 202578 AF XY: 0.540

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.504

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.530

GnomAD4 exome AF: 0.528 AC: 751224 AN: 1422902 Hom.: 200365 Cov.: 41 AF XY: 0.529 AC XY: 373611 AN XY: 706374

African (AFR) AF: 0.616 AC: 20218 AN: 32796

American (AMR) AF: 0.505 AC: 20314 AN: 40188

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 11551 AN: 25618

East Asian (EAS) AF: 0.297 AC: 11234 AN: 37882

South Asian (SAS) AF: 0.563 AC: 46984 AN: 83404

European-Finnish (FIN) AF: 0.535 AC: 23063 AN: 43136

Middle Eastern (MID) AF: 0.551 AC: 3156 AN: 5730

European-Non Finnish (NFE) AF: 0.533 AC: 583766 AN: 1094786

Other (OTH) AF: 0.521 AC: 30938 AN: 59362

GnomAD4 genome AF: 0.534 AC: 80985 AN: 151564 Hom.: 22112 Cov.: 31 AF XY: 0.534 AC XY: 39506 AN XY: 74034

African (AFR) AF: 0.614 AC: 25399 AN: 41334

American (AMR) AF: 0.525 AC: 8011 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1550 AN: 3462

East Asian (EAS) AF: 0.265 AC: 1356 AN: 5120

South Asian (SAS) AF: 0.560 AC: 2690 AN: 4806

European-Finnish (FIN) AF: 0.514 AC: 5398 AN: 10500

Middle Eastern (MID) AF: 0.545 AC: 158 AN: 290

European-Non Finnish (NFE) AF: 0.517 AC: 35053 AN: 67784

Other (OTH) AF: 0.537 AC: 1131 AN: 2108

Alfa AF: 0.424 Hom.: 1976

Bravo AF: 0.536

Asia WGS AF: 0.456 AC: 1585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0030
DANN	Benign	0.16
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.036	T
MetaRNN	Benign	0.0000035	T
MetaSVM	Benign	-0.95	T
PhyloP100		-5.6
PROVEAN	Benign	2.6	N
REVEL	Benign	0.040
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1644698;

hg19: chr19-37488472;

COSMIC: COSV71278458;

COSMIC: COSV71278458;