22-28975773-C-T

Position:

• chr22-28975773-C-T

Variant summary

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

The NM_001206998.2(ZNRF3):​c.301-11303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,894 control chromosomes in the GnomAD database, including 5,861 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 0.25 (5861 hom., cov: 31)
• Consequence: ZNRF3 NM_001206998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNRF3	NM_001206998.2	c.301-11303C>T		intron_variant		ENST00000544604.7
ZNRF3	NM_032173.4	c.1-11303C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNRF3	ENST00000544604.7	c.301-11303C>T		intron_variant		1	NM_001206998.2	A2
ZNRF3	ENST00000402174.5	c.1-11303C>T		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37718 AN: 151776 Hom.: 5860 Cov.: 31

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37704 AN: 151894 Hom.: 5861 Cov.: 31 AF XY: 0.245 AC XY: 18208 AN XY: 74212

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.282

Alfa AF: 0.329 Hom.: 16785

Bravo AF: 0.243

Asia WGS AF: 0.264 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.74
DANN	Benign	0.58

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: rs13055470; hg19: chr22-29371761;