Variant chr7-30285650-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000323037.5(ZNRF2):c.293A>G(p.Gln98Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,269,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

ZNRF2
ENST00000323037.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

Variant links:

Genes affected

ZNRF2 (HGNC:22316): (zinc and ring finger 2) Enables ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Located in cytoplasmic vesicle membrane; nuclear lumen; and plasma membrane. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNRF2 links:

LOC105375218 (HGNC:):

LOC105375218 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20366412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNRF2	NM_147128.4 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant	1/5	ENST00000323037.5	NP_667339.1
LOC105375218	NR_136267.1 linkuse as main transcript	n.26+410T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNRF2	ENST00000323037.5 linkuse as main transcript	c.293A>G	p.Gln98Arg	missense_variant	1/5	1	NM_147128.4	ENSP00000323879	P1
ZNRF2	ENST00000459998.1 linkuse as main transcript	n.77A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000277

AC:

AN:

144650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000272

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1124322

Hom.:

Cov.:

AF XY:

0.0000181

AC XY:

AN XY:

551086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000708

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000852

Gnomad4 OTH exome

AF:

0.0000467

GnomAD4 genome

AF:

0.0000276

AC:

AN:

144794

Hom.:

Cov.:

AF XY:

0.0000283

AC XY:

AN XY:

70740

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000272

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.293A>G (p.Q98R) alteration is located in exon 1 (coding exon 1) of the ZNRF2 gene. This alteration results from a A to G substitution at nucleotide position 293, causing the glutamine (Q) at amino acid position 98 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.70

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.60

REVEL

Benign

0.15

Sift

Benign

0.12

Sift4G

Benign

0.59

Polyphen

0.98

Vest4

0.22

MutPred

0.15

Gain of MoRF binding (P = 0.0139);

MVP

0.093

MPC

1.1

ClinPred

0.76

GERP RS

1.9

Varity_R

0.13

gMVP

0.52

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over