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GeneBe

22-29049480-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001206998.2(ZNRF3):c.1299C>T(p.Cys433=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,604,732 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 32)
Exomes 𝑓: 0.010 ( 84 hom. )

Consequence

ZNRF3
NM_001206998.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.63
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-29049480-C-T is Benign according to our data. Variant chr22-29049480-C-T is described in ClinVar as [Benign]. Clinvar id is 2653040.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.63 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1106 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNRF3NM_001206998.2 linkuse as main transcriptc.1299C>T p.Cys433= synonymous_variant 8/9 ENST00000544604.7
ZNRF3NM_032173.4 linkuse as main transcriptc.999C>T p.Cys333= synonymous_variant 8/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNRF3ENST00000544604.7 linkuse as main transcriptc.1299C>T p.Cys433= synonymous_variant 8/91 NM_001206998.2 A2Q9ULT6-1
ZNRF3ENST00000406323.3 linkuse as main transcriptc.999C>T p.Cys333= synonymous_variant 7/81 P2Q9ULT6-2
ZNRF3ENST00000402174.5 linkuse as main transcriptc.999C>T p.Cys333= synonymous_variant 8/92 P2Q9ULT6-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00727
AC:
1106
AN:
152148
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00174
Gnomad AMI
AF:
0.00877
Gnomad AMR
AF:
0.00955
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00539
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0112
Gnomad OTH
AF:
0.0120
GnomAD3 exomes
AF:
0.00795
AC:
1911
AN:
240294
Hom.:
5
AF XY:
0.00829
AC XY:
1089
AN XY:
131296
show subpopulations
Gnomad AFR exome
AF:
0.00184
Gnomad AMR exome
AF:
0.00733
Gnomad ASJ exome
AF:
0.00683
Gnomad EAS exome
AF:
0.0000562
Gnomad SAS exome
AF:
0.00605
Gnomad FIN exome
AF:
0.00410
Gnomad NFE exome
AF:
0.0114
Gnomad OTH exome
AF:
0.00639
GnomAD4 exome
AF:
0.0104
AC:
15063
AN:
1452466
Hom.:
84
Cov.:
31
AF XY:
0.0104
AC XY:
7502
AN XY:
723016
show subpopulations
Gnomad4 AFR exome
AF:
0.00173
Gnomad4 AMR exome
AF:
0.00757
Gnomad4 ASJ exome
AF:
0.00779
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00584
Gnomad4 FIN exome
AF:
0.00467
Gnomad4 NFE exome
AF:
0.0118
Gnomad4 OTH exome
AF:
0.00945
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00726
AC:
1106
AN:
152266
Hom.:
3
Cov.:
32
AF XY:
0.00690
AC XY:
514
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00173
Gnomad4 AMR
AF:
0.00954
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00540
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.0112
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00929
Hom.:
2
Bravo
AF:
0.00773
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0124
EpiControl
AF:
0.0129

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023ZNRF3: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
Cadd
Benign
4.5
Dann
Benign
0.58

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs34671303; hg19: chr22-29445468; COSMIC: COSV60433235; API