19-51876582-A-G

Position:

• chr19-51876582-A-G

Variant summary

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

The NM_001370449.1(ZNF577):​c.283+700T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,894 control chromosomes in the GnomAD database, including 5,861 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 0.24 (5861 hom., cov: 30)
• Consequence: ZNF577 NM_001370449.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

Genes affected

ZNF577 (HGNC:28673): (zinc finger protein 577) 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF577	NM_001370449.1	c.283+700T>C		intron_variant		ENST00000638348.2	NP_001357378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF577	ENST00000638348.2	c.283+700T>C		intron_variant		2	NM_001370449.1	ENSP00000491936	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36564 AN: 151776 Hom.: 5833 Cov.: 30

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.241 AC: 36640 AN: 151894 Hom.: 5861 Cov.: 30 AF XY: 0.249 AC XY: 18473 AN XY: 74234

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.228

Alfa AF: 0.139 Hom.: 2031

Bravo AF: 0.251

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.58

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: rs3848562; hg19: chr19-52379835;