rs234301

Positions:

• chr19-40016111-A-G

Variant summary

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

The NM_178544.5(ZNF546):​c.*330A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 279,800 control chromosomes in the GnomAD database, including 5,120 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 0.16 (4534 hom., cov: 32)
  • Exomes 𝑓: 0.054 (586 hom.)
• Consequence: ZNF546 NM_178544.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

Genes affected

ZNF546 (HGNC:28671): (zinc finger protein 546) 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 integral component of membrane. 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF546	NM_178544.5	c.*330A>G		3_prime_UTR_variant	7/7	ENST00000347077.9	NP_848639.2
ZNF546	NM_001297763.2	c.*330A>G		3_prime_UTR_variant	7/7		NP_001284692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF546	ENST00000347077.9	c.*330A>G		3_prime_UTR_variant	7/7	1	NM_178544.5	ENSP00000339823.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23790 AN: 151522 Hom.: 4520 Cov.: 32

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.00442

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.0542 AC: 6948 AN: 128162 Hom.: 586 Cov.: 0 AF XY: 0.0566 AC XY: 3875 AN XY: 68462

Gnomad4 AFR exome AF: 0.427

Gnomad4 AMR exome AF: 0.0645

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.0788

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.157 AC: 23858 AN: 151638 Hom.: 4534 Cov.: 32 AF XY: 0.155 AC XY: 11476 AN XY: 74090

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.0912

Gnomad4 FIN AF: 0.0262

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0998 Hom.: 312

Bravo AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.57

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: rs234301; hg19: chr19-40522018;