rs505717

Variant names:

• chr19-36939414-A-G
• rs505717
• NM_198539.4:c.358+2172A>G

Variant summary

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

The NM_198539.4(ZNF568):​c.358+2172A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,970 control chromosomes in the GnomAD database, including 10,263 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 0.36 (10263 hom., cov: 32)
• Consequence: ZNF568 NM_198539.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 6 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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_198539.4	c.358+2172A>G		intron_variant	Intron 6 of 6	ENST00000333987.12	NP_940941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF568	ENST00000333987.12	c.358+2172A>G		intron_variant	Intron 6 of 6	1	NM_198539.4	ENSP00000334685.7
ENSG00000291239	ENST00000706165.1	c.358+2172A>G		intron_variant	Intron 8 of 11			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54999 AN: 151856 Hom.: 10252 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0729

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.355

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.362 AC: 55060 AN: 151970 Hom.: 10263 Cov.: 32 AF XY: 0.359 AC XY: 26669 AN XY: 74256

African (AFR) AF: 0.405 AC: 16781 AN: 41422

American (AMR) AF: 0.354 AC: 5412 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1008 AN: 3470

East Asian (EAS) AF: 0.0734 AC: 380 AN: 5174

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4820

European-Finnish (FIN) AF: 0.331 AC: 3487 AN: 10524

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25551 AN: 67970

Other (OTH) AF: 0.355 AC: 748 AN: 2108

Alfa AF: 0.360 Hom.: 1271

Bravo AF: 0.366

Asia WGS AF: 0.234 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.75
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs505717; hg19: chr19-37430316;