rs3178915

Variant names:

• chr22-29057039-A-G
• rs3178915
• NM_001206998.2:c.*3417A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-29057039-A-G
• chr22-29057039-A-T

Variant summary

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

The NM_001206998.2(ZNRF3):​c.*3417A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,070 control chromosomes in the GnomAD database, including 23,587 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 0.55 (23587 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZNRF3 NM_001206998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• Publications: 16 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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNRF3	NM_001206998.2	c.*3417A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000544604.7	NP_001193927.1
ZNRF3	NM_032173.4	c.*3417A>G		3_prime_UTR_variant	Exon 9 of 9		NP_115549.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNRF3	ENST00000544604.7	c.*3417A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001206998.2	ENSP00000443824.2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84001 AN: 151952 Hom.: 23542 Cov.: 33

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.549

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.553 AC: 84102 AN: 152070 Hom.: 23587 Cov.: 33 AF XY: 0.555 AC XY: 41216 AN XY: 74326

African (AFR) AF: 0.611 AC: 25328 AN: 41480

American (AMR) AF: 0.541 AC: 8266 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2024 AN: 3472

East Asian (EAS) AF: 0.616 AC: 3191 AN: 5180

South Asian (SAS) AF: 0.637 AC: 3073 AN: 4826

European-Finnish (FIN) AF: 0.539 AC: 5677 AN: 10530

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.512 AC: 34821 AN: 67994

Other (OTH) AF: 0.551 AC: 1162 AN: 2108

Alfa AF: 0.528 Hom.: 86879

Bravo AF: 0.552

Asia WGS AF: 0.640 AC: 2225 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3178915; hg19: chr22-29453027;