rs4823006

Variant names:

• chr22-29055683-A-G
• rs4823006
• NM_001206998.2:c.*2061A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-29055683-A-G
• chr22-29055683-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 85 publications found

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]

ZNRF3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNRF3	NM_001206998.2	c.*2061A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000544604.7	NP_001193927.1
ZNRF3	NM_032173.4	c.*2061A>G		3_prime_UTR_variant	Exon 9 of 9		NP_115549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRF3	ENST00000544604.7	c.*2061A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001206998.2	ENSP00000443824.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.667 AC: 4 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.688 AC: 11 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.475 AC: 19 AN: 40

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

African (AFR) AF: 0.294 AC: 12184 AN: 41472

American (AMR) AF: 0.475 AC: 7259 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1920 AN: 3470

East Asian (EAS) AF: 0.564 AC: 2913 AN: 5166

South Asian (SAS) AF: 0.577 AC: 2782 AN: 4820

European-Finnish (FIN) AF: 0.437 AC: 4615 AN: 10562

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29837 AN: 67958

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.439 Hom.: 56744

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
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4823006; hg19: chr22-29451671;