Variant 9-122078-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018491.5(ZNG1A):c.964A>G(p.Ile322Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNG1A
NM_018491.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.907

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 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=0.07798678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.964A>G	p.Ile322Val	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.964A>G	p.Ile322Val	missense_variant	14/15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*562A>G		non_coding_transcript_exon_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*685A>G		non_coding_transcript_exon_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*509A>G		non_coding_transcript_exon_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*562A>G		3_prime_UTR_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*685A>G		3_prime_UTR_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*509A>G		3_prime_UTR_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000165

AC:

AN:

1458660

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151378

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73896

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

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

Alfa

AF:

0.0000712

Hom.:

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

May 08, 2023

The c.964A>G (p.I322V) alteration is located in exon 14 (coding exon 14) of the CBWD1 gene. This alteration results from a A to G substitution at nucleotide position 964, causing the isoleucine (I) at amino acid position 322 to be replaced by a valine (V). 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

0.082

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0028

T;T;.;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.77

.;T;T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.078

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

L;L;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.57

N;.;N;.;N

REVEL

Benign

0.024

Sift

Benign

0.22

T;.;T;.;T

Sift4G

Benign

0.79

T;T;T;T;T

Polyphen

0.044

B;B;B;.;B

Vest4

0.12

MutPred

0.36

Loss of stability (P = 0.0495);Loss of stability (P = 0.0495);.;.;.;

MVP

0.18

ClinPred

0.12

GERP RS

2.9

Varity_R

0.059

gMVP

0.0088

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