19-51835388-T-C

Position:

• chr19-51835388-T-C

Variant summary

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

The ENST00000638827.1(ZNF577):​c.*599+4505A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 150,122 control chromosomes in the GnomAD database, including 156 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 0.041 (156 hom., cov: 31)
• Consequence: ZNF577 ENST00000638827.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF577	NR_163433.1	n.2152+4505A>G		intron_variant, non_coding_transcript_variant
ZNF577	XR_007067019.1	n.2826+4505A>G		intron_variant, non_coding_transcript_variant
ZNF577	XR_007067020.1	n.2826+4505A>G		intron_variant, non_coding_transcript_variant
ZNF577	XR_007067021.1	n.2826+4505A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF577	ENST00000638827.1	c.*599+4505A>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6200 AN: 150012 Hom.: 157 Cov.: 31

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0697

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0529

Gnomad EAS AF: 0.00295

Gnomad SAS AF: 0.0966

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0396

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

GnomAD4 genome AF: 0.0413 AC: 6200 AN: 150122 Hom.: 156 Cov.: 31 AF XY: 0.0417 AC XY: 3059 AN XY: 73296

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0529

Gnomad4 EAS AF: 0.00296

Gnomad4 SAS AF: 0.0971

Gnomad4 FIN AF: 0.0446

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0392

Alfa AF: 0.0391 Hom.: 16

Bravo AF: 0.0377

Asia WGS AF: 0.0470 AC: 165 AN: 3448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.4
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62110082; hg19: chr19-52338641;