chr19-56422742-A-G

Position:

• chr19-56422742-A-G

Variant summary

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

The NM_152478.3(ZNF583):​c.233-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 525,936 control chromosomes in the GnomAD database, including 86,601 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 0.57 (24850 hom., cov: 32)
  • Exomes 𝑓: 0.56 (61751 hom.)
• Consequence: ZNF583 NM_152478.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

Genes affected

ZNF583 (HGNC:26427): (zinc finger protein 583) 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 regulation of transcription by RNA polymerase II. Predicted to be active 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF583	NM_152478.3	c.233-149A>G		intron_variant		ENST00000333201.13	NP_689691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF583	ENST00000333201.13	c.233-149A>G		intron_variant		2	NM_152478.3	ENSP00000388502	P1
ZNF583	ENST00000291598.11	c.233-149A>G		intron_variant		3		ENSP00000291598	P1
ZNF583	ENST00000391778.3	c.233-149A>G		intron_variant		4		ENSP00000375657
ZNF583	ENST00000537943.5	c.233-149A>G		intron_variant		3		ENSP00000444291

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86110 AN: 151862 Hom.: 24801 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.536

GnomAD4 exome AF: 0.564 AC: 211005 AN: 373956 Hom.: 61751 AF XY: 0.565 AC XY: 109499 AN XY: 193970

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.625

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.882

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.524

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.567 AC: 86217 AN: 151980 Hom.: 24850 Cov.: 32 AF XY: 0.572 AC XY: 42494 AN XY: 74286

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.539

Alfa AF: 0.545 Hom.: 3029

Bravo AF: 0.567

Asia WGS AF: 0.739 AC: 2551 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.065
DANN	Benign	0.68

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: rs917652; hg19: chr19-56934111;