chr19-36997597-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000444991.6(ZNF568):​c.1906T>A​(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 0.00000071 in 1,408,556 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000444991.6 Downstream stopcodon found after 809 codons.

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>A	p.Ter636Argext*?	stop_lost	Exon 10 of 10	NP_001191767.1
	ZNF568	NM_001204839.2		c.1714T>A	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>A	p.Ter636Argext*?	stop_lost	Exon 10 of 10	ENSP00000389794.2
	ENSG00000291239	ENST00000706165.1		c.1906T>A	p.Ter636Argext*?	stop_lost	Exon 12 of 12	ENSP00000516244.1
	ZNF568	ENST00000591887.1	TSL:1	n.2075T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408556 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 697842

African (AFR) AF: 0.00 AC: 0 AN: 32280

American (AMR) AF: 0.00 AC: 0 AN: 38056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25432

East Asian (EAS) AF: 0.00 AC: 0 AN: 36870

South Asian (SAS) AF: 0.00 AC: 0 AN: 81730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088600

Other (OTH) AF: 0.00 AC: 0 AN: 58812

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	10
DANN	Benign	0.87
Eigen	Benign	0.18
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.021	N
PhyloP100		-2.8
Vest4		0.0010
GERP RS		2.7
Mutation Taster		=189/11	polymorphism

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;