Variant 9-121975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018491.5(ZNG1A):c.1067G>A(p.Arg356Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000274 in 1,611,718 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZNG1A
NM_018491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Variant links:

Genes affected

ZNG1A (HGNC:17134): (Zn regulated GTPase metalloprotein activator 1A) Predicted to enable ATP binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNG1A links:

ZNG1A (HGNC:):

ZNG1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060367107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.1067G>A	p.Arg356Gln	missense_variant	14/15	ENST00000356521.9	NP_060961.3	Q9BRT8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNG1A	ENST00000356521.9 linkuse as main transcript	c.1067G>A	p.Arg356Gln	missense_variant	14/15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*665G>A		non_coding_transcript_exon_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*788G>A		non_coding_transcript_exon_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*612G>A		non_coding_transcript_exon_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*665G>A		3_prime_UTR_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*788G>A		3_prime_UTR_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*612G>A		3_prime_UTR_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000720

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:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000283

AC:

AN:

197934

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

106892

show subpopulations

Gnomad AFR exome

AF:

0.0000691

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000296

Gnomad OTH exome

AF:

0.000430

GnomAD4 exome

AF:

0.000273

AC:

399

AN:

1459562

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

188

AN XY:

726086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000302

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000276

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000325

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000371

AC:

ExAC

AF:

0.000226

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

May 18, 2023

The c.1067G>A (p.R356Q) alteration is located in exon 14 (coding exon 14) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 1067, causing the arginine (R) at amino acid position 356 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.;T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.90

.;D;D;D;D

M_CAP

Benign

0.0086

MetaRNN

Benign

0.060

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.2

N;.;N;.;N

REVEL

Benign

0.11

Sift

Benign

0.073

T;.;T;.;T

Sift4G

Uncertain

0.050

T;T;T;T;T

Polyphen

0.61

P;P;P;.;P

Vest4

0.25

MVP

0.50

ClinPred

0.083

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.072

gMVP

0.077

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