chr19-58259517-G-A

Variant names:

• chr19-58259517-G-A
• rs260461
• NM_014480.4:c.245-1334G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014480.4(ZNF544):​c.245-1334G>A variant causes a intron 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_014480.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF544	NM_014480.4	c.245-1334G>A		intron_variant	Intron 6 of 6	ENST00000687789.1	NP_055295.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF544	ENST00000687789.1	c.245-1334G>A		intron_variant	Intron 6 of 6		NM_014480.4	ENSP00000510489.1
ENSG00000283515	ENST00000637233.1	n.209+12723G>A		intron_variant	Intron 6 of 11	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.175 AC: 7260 AN: 41514

American (AMR) AF: 0.256 AC: 3901 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2900 AN: 5152

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3138 AN: 10566

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10557 AN: 67998

Other (OTH) AF: 0.182 AC: 385 AN: 2116

Alfa AF: 0.169 Hom.: 12154

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
PhyloP100		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs260461; hg19: chr19-58770883;