NM_001206998.2:c.*1313A>G

Variant names:

• chr22-29054935-A-G
• rs2179129
• NM_001206998.2:c.*1313A>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.*1313A>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 0.348 in 152,748 control chromosomes in the GnomAD database, including 10,420 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 0.35 (10365 hom., cov: 32)
  • Exomes 𝑓: 0.38 (55 hom.)
• Consequence: ZNRF3 NM_001206998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 32 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 = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206998.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRF3	NM_001206998.2	MANE Select	c.*1313A>G		3_prime_UTR	Exon 9 of 9	NP_001193927.1	Q9ULT6-1
	ZNRF3	NM_032173.4		c.*1313A>G		3_prime_UTR	Exon 9 of 9	NP_115549.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNRF3	ENST00000544604.7	TSL:1 MANE Select	c.*1313A>G		3_prime_UTR	Exon 9 of 9	ENSP00000443824.2	Q9ULT6-1
	ZNRF3	ENST00000920449.1		c.*1313A>G		3_prime_UTR	Exon 7 of 7	ENSP00000590508.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52902 AN: 151932 Hom.: 10353 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.400

GnomAD4 exome AF: 0.380 AC: 265 AN: 698 Hom.: 55 Cov.: 0 AF XY: 0.389 AC XY: 154 AN XY: 396

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.380 AC: 212 AN: 558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.406 AC: 26 AN: 64

Other (OTH) AF: 0.359 AC: 23 AN: 64

GnomAD4 genome AF: 0.348 AC: 52927 AN: 152050 Hom.: 10365 Cov.: 32 AF XY: 0.352 AC XY: 26136 AN XY: 74314

African (AFR) AF: 0.165 AC: 6866 AN: 41492

American (AMR) AF: 0.420 AC: 6419 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2383 AN: 5168

South Asian (SAS) AF: 0.485 AC: 2335 AN: 4816

European-Finnish (FIN) AF: 0.379 AC: 3995 AN: 10552

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27844 AN: 67966

Other (OTH) AF: 0.403 AC: 853 AN: 2116

Alfa AF: 0.398 Hom.: 21774

Bravo AF: 0.341

Asia WGS AF: 0.443 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.13
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: rs2179129; hg19: chr22-29450923; COSMIC: COSV53310088; COSMIC: COSV53310088;