Variant 9-122029-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_018491.5(ZNG1A):c.1013A>G(p.Tyr338Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000454 in 152,076 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 0.00045 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 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: 5.33

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 -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2795356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.1013A>G	p.Tyr338Cys	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.1013A>G	p.Tyr338Cys	missense_variant	14/15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*611A>G		non_coding_transcript_exon_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*734A>G		non_coding_transcript_exon_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*558A>G		non_coding_transcript_exon_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 linkuse as main transcript	n.*611A>G		3_prime_UTR_variant	14/15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 linkuse as main transcript	n.*734A>G		3_prime_UTR_variant	15/16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000619157.4 linkuse as main transcript	n.*558A>G		3_prime_UTR_variant	11/12	5		ENSP00000483746.1	A0A087X0Y9

Frequencies

GnomAD3 genomes

AF:

0.000461

AC:

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000115

AC:

AN:

78144

Hom.:

AF XY:

0.0000525

AC XY:

AN XY:

38076

show subpopulations

Gnomad AFR exome

AF:

0.000935

Gnomad AMR exome

AF:

0.0000889

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:

0.0000327

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000110

AC:

160

AN:

1458910

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

725720

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.000454

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000590

Hom.:

Bravo

AF:

0.000582

ExAC

AF:

0.0000248

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 01, 2023

The c.1013A>G (p.Y338C) 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 1013, causing the tyrosine (Y) at amino acid position 338 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

Uncertain

0.41

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.041

T;T;.;T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

.;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.5

M;M;.;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.2

D;.;D;.;D

REVEL

Benign

0.29

Sift

Benign

0.055

T;.;T;.;T

Sift4G

Uncertain

0.053

T;T;T;T;T

Polyphen

0.46

P;P;P;.;B

Vest4

0.85

MVP

0.47

ClinPred

0.19

GERP RS

2.9

Varity_R

0.64

gMVP

0.049

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