rs134555

Positions:

• chr22-29025450-A-G
• chr22-29025450-A-T

Variant summary

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

The NM_001206998.2(ZNRF3):​c.427-17045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,308 control chromosomes in the GnomAD database, including 75,404 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 1.0 (75387 hom., cov: 31)
  • Exomes 𝑓: 1.0 (17 hom.)
• Consequence: ZNRF3 NM_001206998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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-AS1 (HGNC:41927): (ZNRF3 antisense RNA 1)

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 (SAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNRF3	NM_001206998.2	c.427-17045A>G		intron_variant		ENST00000544604.7	NP_001193927.1
ZNRF3-AS1	NR_046851.1	n.1719T>C		non_coding_transcript_exon_variant	3/3
ZNRF3	NM_032173.4	c.127-17045A>G		intron_variant			NP_115549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNRF3	ENST00000544604.7	c.427-17045A>G		intron_variant		1	NM_001206998.2	ENSP00000443824	A2
ZNRF3	ENST00000406323.3	c.127-17045A>G		intron_variant		1		ENSP00000384553	P2
ZNRF3-AS1	ENST00000325660.3	n.1719T>C		non_coding_transcript_exon_variant	3/3	2
ZNRF3	ENST00000402174.5	c.127-17045A>G		intron_variant		2		ENSP00000384456	P2

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151403 AN: 152156 Hom.: 75328 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.996

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.999

GnomAD4 exome AF: 1.00 AC: 34 AN: 34 Hom.: 17 Cov.: 0 AF XY: 1.00 AC XY: 30 AN XY: 30

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.995 AC: 151521 AN: 152274 Hom.: 75387 Cov.: 31 AF XY: 0.995 AC XY: 74106 AN XY: 74444

Gnomad4 AFR AF: 0.998

Gnomad4 AMR AF: 0.996

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.999

Alfa AF: 0.993 Hom.: 9459

Bravo AF: 0.995

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.087
DANN	Benign	0.47

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: rs134555; hg19: chr22-29421438;