rs5762919

Positions:

• chr22-28967356-T-C

Variant summary

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

The NM_001206998.2(ZNRF3):​c.301-19720T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,196 control chromosomes in the GnomAD database, including 1,171 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 0.10 (1171 hom., cov: 31)
• Consequence: ZNRF3 NM_001206998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNRF3	NM_001206998.2	c.301-19720T>C		intron_variant		ENST00000544604.7
ZNRF3	NM_032173.4	c.1-19720T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNRF3	ENST00000544604.7	c.301-19720T>C		intron_variant		1	NM_001206998.2	A2
ZNRF3	ENST00000402174.5	c.1-19720T>C		intron_variant		2		P2

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15185 AN: 152078 Hom.: 1159 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0754

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0834

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

GnomAD4 genome AF: 0.100 AC: 15236 AN: 152196 Hom.: 1171 Cov.: 31 AF XY: 0.102 AC XY: 7588 AN XY: 74416

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.0758

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0651 Hom.: 164

Bravo AF: 0.104

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.33

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: rs5762919; hg19: chr22-29363344;