Variant 9-65679222-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001330668.2(ZNG1E):c.211G>A(p.Val71Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 17)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNG1E
NM_001330668.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

ZNG1E (HGNC:24584): (Zn regulated GTPase metalloprotein activator 1E) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNG1E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039147466).

BP6

Variant 9-65679222-G-A is Benign according to our data. Variant chr9-65679222-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2467339.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1E	NM_001330668.2 linkuse as main transcript	c.211G>A	p.Val71Ile	missense_variant	2/15	ENST00000382405.8	NP_001317597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1E	ENST00000382405.8 linkuse as main transcript	c.211G>A	p.Val71Ile	missense_variant	2/15	1	NM_001330668.2	ENSP00000371842	P1	Q5RIA9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

133212

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000491

Gnomad ASJ

AF:

0.00241

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000628

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000138

AC:

AN:

507388

Hom.:

Cov.:

AF XY:

0.000133

AC XY:

AN XY:

263850

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.000297

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000536

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000355

Gnomad4 OTH exome

AF:

0.000376

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000593

AC:

AN:

133294

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

AN XY:

63502

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.000490

Gnomad4 ASJ

AF:

0.00241

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000628

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000759

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_noAF

Benign

-0.28

CADD

Benign

2.4

DANN

Benign

0.46

DEOGEN2

Benign

0.0099

T;.;.;.;.

LIST_S2

Uncertain

0.89

D;D;D;D;D

MetaRNN

Benign

0.039

T;T;T;T;T

PROVEAN

Benign

0.62

N;N;N;N;N

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Vest4

0.17

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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