dbSNP rs134555: ZNRF3:c.427-17045A>G (chr22-29025450-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

1 publications found

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]

ZNRF3 links:

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

ZNRF3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein
ZNRF3	NM_001206998.2 link	c.427-17045A>G	intron_variant	Intron 2 of 8	ENST00000544604.7	NP_001193927.1
ZNRF3-AS1	NR_046851.1 link	n.1719T>C	non_coding_transcript_exon_variant	Exon 3 of 3
ZNRF3	NM_032173.4 link	c.127-17045A>G	intron_variant	Intron 2 of 8		NP_115549.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ZNRF3	ENST00000544604.7 link	c.427-17045A>G	intron_variant	Intron 2 of 8	1	NM_001206998.2	ENSP00000443824.2
ZNRF3	ENST00000406323.3 link	c.127-17045A>G	intron_variant	Intron 1 of 7	1		ENSP00000384553.3
ZNRF3-AS1	ENST00000325660.3 link	n.1719T>C	non_coding_transcript_exon_variant	Exon 3 of 3	2
ZNRF3	ENST00000402174.5 link	c.127-17045A>G	intron_variant	Intron 2 of 8	2		ENSP00000384456.1

Frequencies

GnomAD3 genomes

AF:

0.995

AC:

151403

AN:

152156

Hom.:

75328

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.995

AC:

151521

AN:

152274

Hom.:

75387

Cov.:

AF XY:

0.995

AC XY:

74106

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.998

AC:

41455

AN:

41538

American (AMR)

AF:

0.996

AC:

15242

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5189

AN:

5190

South Asian (SAS)

AF:

1.00

AC:

4820

AN:

4820

European-Finnish (FIN)

AF:

0.999

AC:

10598

AN:

10612

Middle Eastern (MID)

AF:

1.00

AC:

294

AN:

294

European-Non Finnish (NFE)

AF:

0.991

AC:

67432

AN:

68030

Other (OTH)

AF:

0.999

AC:

2107

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.47

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over