Variant chr9-135013-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000356521.9(ZNG1A):c.782A>T(p.Gln261Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.00014 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

ZNG1A
ENST00000356521.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

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:

LOC105375942 (HGNC:):

LOC105375942 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.122250885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNG1A	NM_018491.5 linkuse as main transcript	c.782A>T	p.Gln261Leu	missense_variant	11/15	ENST00000356521.9	NP_060961.3
LOC105375942	XR_929381.2 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNG1A	ENST00000356521.9 linkuse as main transcript	c.782A>T	p.Gln261Leu	missense_variant	11/15	1	NM_018491.5	ENSP00000348915	P1	Q9BRT8-1

Frequencies

GnomAD3 genomes

AF:

0.000142

AC:

AN:

140794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000709

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:

0.000292

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

65128

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

33382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000317

AC:

410

AN:

1291372

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

207

AN XY:

643000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000616

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:

0.000393

Gnomad4 OTH exome

AF:

0.000333

GnomAD4 genome

AF:

0.000142

AC:

AN:

140794

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

68102

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000709

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000292

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000102

ExAC

AF:

0.000107

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

Jul 09, 2021

The c.782A>T (p.Q261L) alteration is located in exon 11 (coding exon 11) of the CBWD1 gene. This alteration results from a A to T substitution at nucleotide position 782, causing the glutamine (Q) at amino acid position 261 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.055

T;T;.;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.76

.;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.0

D;.;D;.;D

REVEL

Benign

0.17

Sift

Benign

0.11

T;.;T;.;T

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.0

B;B;B;.;B

Vest4

0.36

MutPred

0.41

Loss of disorder (P = 0.0366);Loss of disorder (P = 0.0366);.;.;.;

MVP

0.63

ClinPred

0.17

GERP RS

2.8

Varity_R

0.16

gMVP

0.032

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