chr22-29057205-G-C

Position:

• chr22-29057205-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001206998.2(ZNRF3):​c.*3583G>C variant causes a 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,930 control chromosomes in the GnomAD database, including 12,179 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 0.39 (12179 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZNRF3 NM_001206998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNRF3	NM_001206998.2	c.*3583G>C		3_prime_UTR_variant	9/9	ENST00000544604.7	NP_001193927.1
ZNRF3	NM_032173.4	c.*3583G>C		3_prime_UTR_variant	9/9		NP_115549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNRF3	ENST00000544604.7	c.*3583G>C		3_prime_UTR_variant	9/9	1	NM_001206998.2	ENSP00000443824.2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59224 AN: 151812 Hom.: 12159 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.426

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.390 AC: 59265 AN: 151930 Hom.: 12179 Cov.: 33 AF XY: 0.394 AC XY: 29228 AN XY: 74248

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.429

Alfa AF: 0.245 Hom.: 602

Bravo AF: 0.385

Asia WGS AF: 0.468 AC: 1617 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12321; hg19: chr22-29453193;