rs17638989

chr19-12549580-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144976.4(ZNF564):c.3+1750A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,086 control chromosomes in the GnomAD database, including 16,828 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 0.45 (16828 hom., cov: 32)
• Consequence: ZNF564 NM_144976.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

Genes affected

ZNF564 (HGNC:31106): (zinc finger protein 564) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF564	NM_144976.4	c.3+1750A>G		intron_variant		ENST00000339282.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF564	ENST00000339282.12	c.3+1750A>G		intron_variant		1	NM_144976.4	P1
ZNF564	ENST00000416136.1	c.4-718A>G		intron_variant		3
ZNF564	ENST00000596193.1	c.-207+1750A>G		intron_variant		4
ZNF564	ENST00000427105.1	c.193+883A>G		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68554 AN: 151968 Hom.: 16814 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.451 AC: 68594 AN: 152086 Hom.: 16828 Cov.: 32 AF XY: 0.444 AC XY: 33021 AN XY: 74324

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.465

Alfa AF: 0.497 Hom.: 6175

Bravo AF: 0.435

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.6
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs17638989; hg19: chr19-12660394;