rs4823006

chr22-29055683-A-Gchr22-29055683-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001206998.2(ZNRF3):c.*2061A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.414 in 152,100 control chromosomes in the GnomAD database, including 13,699 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 0.41 (13691 hom., cov: 32)
  • Exomes 𝑓: 0.53 (8 hom.)
• Consequence: ZNRF3 NM_001206998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

Genes affected

ZNRF3 (HGNC:18126): (zinc and ring finger 3) Enables frizzled binding activity and ubiquitin-protein transferase activity. Involved in cellular protein metabolic process and negative regulation of Wnt signaling pathway. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNRF3	NM_001206998.2	c.*2061A>G		3_prime_UTR_variant	9/9	ENST00000544604.7
ZNRF3	NM_032173.4	c.*2061A>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNRF3	ENST00000544604.7	c.*2061A>G		3_prime_UTR_variant	9/9	1	NM_001206998.2	A2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62922 AN: 151914 Hom.: 13673 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.529 AC: 36 AN: 68 Hom.: 8 Cov.: 0 AF XY: 0.521 AC XY: 25 AN XY: 48

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.414 AC: 62968 AN: 152032 Hom.: 13691 Cov.: 32 AF XY: 0.421 AC XY: 31253 AN XY: 74318

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.451

Alfa AF: 0.448 Hom.: 22230

Bravo AF: 0.408

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	18
Dann	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4823006; hg19: chr22-29451671;