Variant 9-68299579-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000360171.11(ZNG1C):c.1180T>A(p.Cys394Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNG1C
ENST00000360171.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.913

Variant links:

Genes affected

ZNG1C (HGNC:18519): (Zn regulated GTPase metalloprotein activator 1C) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNG1C links:

ZNG1C (HGNC:):

ZNG1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19344938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1C	NM_201453.4 linkuse as main transcript	c.1180T>A	p.Cys394Ser	missense_variant	15/15	ENST00000360171.11	NP_958861.2	Q5JTY5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1C	ENST00000360171.11 linkuse as main transcript	c.1180T>A	p.Cys394Ser	missense_variant	15/15	1	NM_201453.4	ENSP00000353295.6		Q5JTY5-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143124

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000142

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000308

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000564

Gnomad OTH

AF:

0.00106

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000109

AC:

AN:

450928

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

238798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000298

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.000153

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000314

AC:

AN:

143124

Hom.:

Cov.:

AF XY:

0.000318

AC XY:

AN XY:

69222

show subpopulations

Gnomad4 AFR

AF:

0.0000264

Gnomad4 AMR

AF:

0.000142

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000308

Gnomad4 NFE

AF:

0.000564

Gnomad4 OTH

AF:

0.00106

Alfa

AF:

0.000674

Hom.:

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

Dec 26, 2023

The c.1180T>A (p.C394S) alteration is located in exon 15 (coding exon 15) of the CBWD3 gene. This alteration results from a T to A substitution at nucleotide position 1180, causing the cysteine (C) at amino acid position 394 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

0.036

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;N;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.2

N;.;.

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.23

MutPred

0.49

Gain of glycosylation at C394 (P = 0.0113);.;.;

MVP

0.20

MPC

2.3

ClinPred

0.94

GERP RS

3.9

Varity_R

0.76

gMVP

0.33

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