Variant 9-122030-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_018491.5(ZNG1A):c.1012T>C(p.Tyr338His) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000021 ( 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: 6.38

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 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.1012T>C	p.Tyr338His	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.1012T>C	p.Tyr338His	missense_variant	14/15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*610T>C		non_coding_transcript_exon_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*733T>C		non_coding_transcript_exon_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*557T>C		non_coding_transcript_exon_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*610T>C		3_prime_UTR_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*733T>C		3_prime_UTR_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*557T>C		3_prime_UTR_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151904

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000257

AC:

AN:

77880

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37962

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000206

AC:

AN:

1458946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000899

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

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:

0.000337

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000249

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

Dec 28, 2023

The c.1012T>C (p.Y338H) alteration is located in exon 14 (coding exon 14) of the CBWD1 gene. This alteration results from a T to C substitution at nucleotide position 1012, causing the tyrosine (Y) at amino acid position 338 to be replaced by a histidine (H). 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

0.73

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;T;.;T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

.;D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.78

D;D;D;D;D

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.5

M;M;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

D;.;D;.;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0030

D;.;D;.;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;D;D;.;D

Vest4

0.82

MutPred

0.70

Gain of disorder (P = 0.0189);Gain of disorder (P = 0.0189);.;.;.;

MVP

0.64

ClinPred

0.93

GERP RS

2.9

Varity_R

0.63

gMVP

0.064

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