19-56424158-A-G

Position:

• chr19-56424158-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152478.3(ZNF583):​c.1500A>G​(p.Ala500=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,613,570 control chromosomes in the GnomAD database, including 241,419 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 0.56 (24461 hom., cov: 32)
  • Exomes 𝑓: 0.54 (216958 hom.)
• Consequence: ZNF583 NM_152478.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF583	NM_152478.3	c.1500A>G	p.Ala500=	synonymous_variant	5/5	ENST00000333201.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF583	ENST00000333201.13	c.1500A>G	p.Ala500=	synonymous_variant	5/5	2	NM_152478.3	P1
ZNF583	ENST00000585612.1	n.653+356A>G		intron_variant, non_coding_transcript_variant		1
ZNF583	ENST00000291598.11	c.1500A>G	p.Ala500=	synonymous_variant	5/5	3		P1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85454 AN: 151888 Hom.: 24419 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.532

GnomAD3 exomes AF: 0.577 AC: 144701 AN: 250734 Hom.: 43025 AF XY: 0.569 AC XY: 77141 AN XY: 135520

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.879

Gnomad SAS exome AF: 0.602

Gnomad FIN exome AF: 0.607

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.540 AC: 789042 AN: 1461564 Hom.: 216958 Cov.: 53 AF XY: 0.540 AC XY: 392639 AN XY: 727084

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.642

Gnomad4 ASJ exome AF: 0.436

Gnomad4 EAS exome AF: 0.878

Gnomad4 SAS exome AF: 0.595

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.542

GnomAD4 genome AF: 0.563 AC: 85552 AN: 152006 Hom.: 24461 Cov.: 32 AF XY: 0.568 AC XY: 42161 AN XY: 74290

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.535

Alfa AF: 0.515 Hom.: 37267

Bravo AF: 0.562

Asia WGS AF: 0.738 AC: 2562 AN: 3478

EpiCase AF: 0.505

EpiControl AF: 0.494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.9
DANN	Benign	0.79

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: rs3810340; hg19: chr19-56935527;