19-36997597-T-C

Variant names:

• chr19-36997597-T-C
• rs1667366
• ENST00000444991.6:c.1906T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM4 BA1

The ENST00000444991.6(ZNF568):​c.1906T>C​(p.Ter636Argext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,549,972 control chromosomes in the GnomAD database, including 219,692 homozygotes. In-silico tool predicts 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 (22086 hom., cov: 31)
  • Exomes 𝑓: 0.53 (197606 hom.)
• Consequence: ZNF568 ENST00000444991.6 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 19 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: Likely_benign. The variant received -6 ACMG points.

• PM4: Stoplost variant in ENST00000444991.6 Downstream stopcodon found after 809 codons.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF568	NM_001204838.2		c.1906T>C	p.Ter636Argext*?	stop_lost	Exon 10 of 10	NP_001191767.1
	ZNF568	NM_001204839.2		c.1714T>C	p.Ter572Argext*?	stop_lost	Exon 9 of 9	NP_001191768.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF568	ENST00000444991.6	TSL:1	c.1906T>C	p.Ter636Argext*?	stop_lost	Exon 10 of 10	ENSP00000389794.2
	ENSG00000291239	ENST00000706165.1		c.1906T>C	p.Ter636Argext*?	stop_lost	Exon 12 of 12	ENSP00000516244.1
	ZNF568	ENST00000591887.1	TSL:1	n.2075T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80827 AN: 151346 Hom.: 22052 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.538 AC: 96479 AN: 179314 AF XY: 0.542

Gnomad AFR exome AF: 0.658

Gnomad AMR exome AF: 0.501

Gnomad ASJ exome AF: 0.456

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.528 AC: 737866 AN: 1398508 Hom.: 197606 Cov.: 34 AF XY: 0.529 AC XY: 366506 AN XY: 693294

African (AFR) AF: 0.616 AC: 19797 AN: 32122

American (AMR) AF: 0.504 AC: 19189 AN: 38044

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11412 AN: 25352

East Asian (EAS) AF: 0.297 AC: 10950 AN: 36836

South Asian (SAS) AF: 0.562 AC: 45861 AN: 81534

European-Finnish (FIN) AF: 0.534 AC: 21922 AN: 41058

Middle Eastern (MID) AF: 0.551 AC: 3124 AN: 5674

European-Non Finnish (NFE) AF: 0.533 AC: 575151 AN: 1079428

Other (OTH) AF: 0.521 AC: 30460 AN: 58460

GnomAD4 genome AF: 0.534 AC: 80922 AN: 151464 Hom.: 22086 Cov.: 31 AF XY: 0.533 AC XY: 39461 AN XY: 73968

African (AFR) AF: 0.614 AC: 25379 AN: 41314

American (AMR) AF: 0.525 AC: 7990 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1549 AN: 3462

East Asian (EAS) AF: 0.266 AC: 1358 AN: 5114

South Asian (SAS) AF: 0.559 AC: 2679 AN: 4796

European-Finnish (FIN) AF: 0.513 AC: 5384 AN: 10486

Middle Eastern (MID) AF: 0.542 AC: 156 AN: 288

European-Non Finnish (NFE) AF: 0.517 AC: 35061 AN: 67776

Other (OTH) AF: 0.537 AC: 1129 AN: 2104

Alfa AF: 0.512 Hom.: 32002

Bravo AF: 0.536

TwinsUK AF: 0.535 AC: 1983

ALSPAC AF: 0.553 AC: 2132

ExAC AF: 0.498 AC: 57311

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
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.87
Eigen	Benign	0.18
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.0017	N
PhyloP100		-2.8
Vest4		0.0010
GERP RS		2.7
Mutation Taster		=189/11	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1667366; hg19: chr19-37488499; COSMIC: COSV71278460; COSMIC: COSV71278460;