rs234301

Variant names:

• chr19-40016111-A-G
• rs234301
• NM_178544.5:c.*330A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178544.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF546	NM_178544.5	MANE Select	c.*330A>G		3_prime_UTR	Exon 7 of 7	NP_848639.2	Q86UE3
	ZNF546	NM_001297763.2		c.*330A>G		3_prime_UTR	Exon 7 of 7	NP_001284692.1	M0QY24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF546	ENST00000347077.9	TSL:1 MANE Select	c.*330A>G		3_prime_UTR	Exon 7 of 7	ENSP00000339823.3	Q86UE3
	ZNF546	ENST00000600094.5	TSL:2	c.*330A>G		3_prime_UTR	Exon 7 of 7	ENSP00000469540.1	M0QY24
	ZNF546	ENST00000951738.1		c.*330A>G		3_prime_UTR	Exon 7 of 7	ENSP00000621797.1

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

African (AFR) AF: 0.427 AC: 1447 AN: 3386

American (AMR) AF: 0.0645 AC: 331 AN: 5132

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 426 AN: 3546

East Asian (EAS) AF: 0.155 AC: 913 AN: 5904

South Asian (SAS) AF: 0.0788 AC: 1484 AN: 18828

European-Finnish (FIN) AF: 0.0224 AC: 125 AN: 5584

Middle Eastern (MID) AF: 0.0529 AC: 24 AN: 454

European-Non Finnish (NFE) AF: 0.0226 AC: 1776 AN: 78578

Other (OTH) AF: 0.0625 AC: 422 AN: 6750

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

African (AFR) AF: 0.451 AC: 18628 AN: 41330

American (AMR) AF: 0.0750 AC: 1143 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.178 AC: 914 AN: 5134

South Asian (SAS) AF: 0.0912 AC: 436 AN: 4782

European-Finnish (FIN) AF: 0.0262 AC: 276 AN: 10550

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0255 AC: 1733 AN: 67838

Other (OTH) AF: 0.136 AC: 287 AN: 2104

Alfa AF: 0.0998 Hom.: 312

Bravo AF: 0.173

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.9
DANN	Benign	0.57
PhyloP100		0.13
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs234301; hg19: chr19-40522018;