rs260461

Positions:

• chr19-58259517-G-A
• chr19-58259517-G-C

Variant summary

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

The NM_001387429.1(ZNF544):​c.*235G>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 0.197 in 152,112 control chromosomes in the GnomAD database, including 3,594 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 0.20 (3594 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF544 NM_001387429.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

Genes affected

ZNF544 (HGNC:16759): (zinc finger protein 544) Predicted to enable DNA-binding transcription activator 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]

ENSG00000283515 (HGNC:):

ZNF8-DT (HGNC:55280): (ZNF8 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.245-1334G>A		intron_variant		ENST00000687789.1	NP_055295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1	c.245-1334G>A		intron_variant			NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.209+12723G>A		intron_variant		5		ENSP00000490395.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29981 AN: 151996 Hom.: 3596 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.178

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.197 AC: 29990 AN: 152112 Hom.: 3594 Cov.: 32 AF XY: 0.209 AC XY: 15509 AN XY: 74356

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.182

Alfa AF: 0.167 Hom.: 5802

Bravo AF: 0.187

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs260461; hg19: chr19-58770883;