chr19-56424158-A-G

Variant names:

• chr19-56424158-A-G
• rs3810340
• NM_152478.3:c.1500A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_152478.3(ZNF583):​c.1500A>G​(p.Ala500Ala) 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152478.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF583	NM_152478.3	MANE Select	c.1500A>G	p.Ala500Ala	synonymous	Exon 5 of 5	NP_689691.2
	ZNF583	NM_001159860.2		c.1500A>G	p.Ala500Ala	synonymous	Exon 5 of 5	NP_001153332.1
	ZNF583	NM_001159861.2		c.1500A>G	p.Ala500Ala	synonymous	Exon 5 of 5	NP_001153333.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF583	ENST00000333201.13	TSL:2 MANE Select	c.1500A>G	p.Ala500Ala	synonymous	Exon 5 of 5	ENSP00000388502.2
	ZNF583	ENST00000585612.1	TSL:1	n.653+356A>G		intron	N/A
	ZNF583	ENST00000291598.11	TSL:3	c.1500A>G	p.Ala500Ala	synonymous	Exon 5 of 5	ENSP00000291598.7

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

GnomAD2 exomes AF: 0.577 AC: 144701 AN: 250734 AF XY: 0.569

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 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

African (AFR) AF: 0.567 AC: 18987 AN: 33474

American (AMR) AF: 0.642 AC: 28730 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 11381 AN: 26126

East Asian (EAS) AF: 0.878 AC: 34857 AN: 39684

South Asian (SAS) AF: 0.595 AC: 51361 AN: 86252

European-Finnish (FIN) AF: 0.610 AC: 32464 AN: 53256

Middle Eastern (MID) AF: 0.416 AC: 2398 AN: 5766

European-Non Finnish (NFE) AF: 0.518 AC: 576149 AN: 1111896

Other (OTH) AF: 0.542 AC: 32715 AN: 60390

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

African (AFR) AF: 0.572 AC: 23714 AN: 41466

American (AMR) AF: 0.604 AC: 9238 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1482 AN: 3464

East Asian (EAS) AF: 0.879 AC: 4545 AN: 5172

South Asian (SAS) AF: 0.625 AC: 3008 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6416 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.519 AC: 35280 AN: 67928

Other (OTH) AF: 0.535 AC: 1128 AN: 2110

Alfa AF: 0.524 Hom.: 61962

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		-2.2
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: rs3810340; hg19: chr19-56935527; COSMIC: COSV108082997; COSMIC: COSV108082997;