rs1667366

Positions:

• chr19-36997597-T-A
• chr19-36997597-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001204838.2(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 NM_001204838.2 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001204838.2 Downstream stopcodon found after 806 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1906T>A	p.Ter636Argext*?	stop_lost	10/10		NP_001191767.1
ZNF568	NM_001204839.2	c.1714T>A	p.Ter572Argext*?	stop_lost	9/9		NP_001191768.1
ZNF568	XM_017026772.2	c.1906T>A	p.Ter636Argext*?	stop_lost	10/10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1906T>A	p.Ter636Argext*?	stop_lost	12/12			ENSP00000516244.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.19e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
Vest4		0.0010
GERP RS		2.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1667366; hg19: chr19-37488499;