rs10483153

Variant names:

• chr22-29006763-A-G
• rs10483153
• NM_001206998.2:c.426+19562A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206998.2(ZNRF3):​c.426+19562A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,306 control chromosomes in the GnomAD database, including 46 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 0.015 (46 hom., cov: 32)
• Consequence: ZNRF3 NM_001206998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 1 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-IT1 (HGNC:41440): (ZNRF3 intronic transcript 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNRF3	NM_001206998.2	c.426+19562A>G		intron_variant	Intron 2 of 8	ENST00000544604.7	NP_001193927.1
ZNRF3	NM_032173.4	c.126+19562A>G		intron_variant	Intron 2 of 8		NP_115549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRF3	ENST00000544604.7	c.426+19562A>G		intron_variant	Intron 2 of 8	1	NM_001206998.2	ENSP00000443824.2
ZNRF3	ENST00000406323.3	c.126+19562A>G		intron_variant	Intron 1 of 7	1		ENSP00000384553.3
ZNRF3	ENST00000402174.5	c.126+19562A>G		intron_variant	Intron 2 of 8	2		ENSP00000384456.1
ZNRF3-IT1	ENST00000412798.1	n.218-11401A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2328 AN: 152188 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.0536

Gnomad SAS AF: 0.0586

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.0153 AC: 2337 AN: 152306 Hom.: 46 Cov.: 32 AF XY: 0.0177 AC XY: 1318 AN XY: 74486

African (AFR) AF: 0.00407 AC: 169 AN: 41568

American (AMR) AF: 0.0351 AC: 537 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.0541 AC: 281 AN: 5192

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4828

European-Finnish (FIN) AF: 0.0322 AC: 342 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 680 AN: 68014

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0149 Hom.: 3

Bravo AF: 0.0156

Asia WGS AF: 0.0470 AC: 162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.75
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10483153; hg19: chr22-29402751;