Variant 9-68299009-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000360171.11(ZNG1C):c.997G>T(p.Gly333Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,609,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZNG1C
ENST00000360171.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3620292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1C	NM_201453.4 linkuse as main transcript	c.997G>T	p.Gly333Cys	missense_variant	14/15	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.997G>T	p.Gly333Cys	missense_variant	14/15	1	NM_201453.4	ENSP00000353295.6		Q5JTY5-1

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000777

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

GnomAD3 exomes

AF:

0.0000827

AC:

AN:

84670

Hom.:

AF XY:

0.0000925

AC XY:

AN XY:

43236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000689

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1458454

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

725458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000857

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151090

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73688

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000777

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

ExAC

AF:

0.0000460

AC:

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

Sep 13, 2023

The c.997G>T (p.G333C) alteration is located in exon 14 (coding exon 14) of the CBWD3 gene. This alteration results from a G to T substitution at nucleotide position 997, causing the glycine (G) at amino acid position 333 to be replaced by a cysteine (C). 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;.;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.084

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.1

M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-5.1

D;.;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.023

D;.;.

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.93

P;.;.

Vest4

0.83

MutPred

0.85

Gain of sheet (P = 0.0827);.;.;

MVP

0.45

MPC

2.2

ClinPred

0.46

GERP RS

3.5

Varity_R

0.73

gMVP

0.76

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