19-57491451-T-A

Position:

• chr19-57491451-T-A

Variant summary

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

The NM_024691.4(ZNF419):​c.73-20T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 1,610,894 control chromosomes in the GnomAD database, including 395,717 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 0.67 (34517 hom., cov: 30)
  • Exomes 𝑓: 0.70 (361200 hom.)
• Consequence: ZNF419 NM_024691.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125

Genes affected

ZNF419 (HGNC:20648): (zinc finger protein 419) 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]

ZNF419 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF419	NM_024691.4	c.73-20T>A		intron_variant		ENST00000221735.12	NP_078967.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF419	ENST00000221735.12	c.73-20T>A		intron_variant		1	NM_024691.4	ENSP00000221735.7
ENSG00000268107	ENST00000601674.6	n.34-20T>A		intron_variant		2		ENSP00000471625.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102129 AN: 151734 Hom.: 34489 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.646

GnomAD3 exomes AF: 0.711 AC: 178385 AN: 250882 Hom.: 63875 AF XY: 0.715 AC XY: 96913 AN XY: 135592

Gnomad AFR exome AF: 0.601

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.662

Gnomad EAS exome AF: 0.718

Gnomad SAS exome AF: 0.790

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.703 AC: 1025142 AN: 1459040 Hom.: 361200 Cov.: 58 AF XY: 0.704 AC XY: 510712 AN XY: 725304

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.789

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.697

Gnomad4 OTH exome AF: 0.695

GnomAD4 genome AF: 0.673 AC: 102210 AN: 151854 Hom.: 34517 Cov.: 30 AF XY: 0.675 AC XY: 50090 AN XY: 74210

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.645

Alfa AF: 0.680 Hom.: 6514

Bravo AF: 0.667

Asia WGS AF: 0.761 AC: 2645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.7
DANN	Benign	0.72

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: rs6510085; hg19: chr19-58002819;