19-51869723-C-T

Position:

• chr19-51869723-C-T

Variant summary

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

The NM_001370449.1(ZNF577):​c.*2809G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,138 control chromosomes in the GnomAD database, including 3,923 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 0.21 (3923 hom., cov: 32)
• Consequence: ZNF577 NM_001370449.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF577	NM_001370449.1	c.*2809G>A		3_prime_UTR_variant	6/6	ENST00000638348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF577	ENST00000638348.2	c.*2809G>A		3_prime_UTR_variant	6/6	2	NM_001370449.1	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31427 AN: 152020 Hom.: 3908 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.207 AC: 31481 AN: 152138 Hom.: 3923 Cov.: 32 AF XY: 0.214 AC XY: 15952 AN XY: 74384

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.202

Alfa AF: 0.135 Hom.: 2542

Bravo AF: 0.211

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.6
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10411161; hg19: chr19-52372976; COSMIC: COSV56814621;