Genetic Variant NM_018491.5:c.929G>A (chr9-123239-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018491.5(ZNG1A):c.929G>A(p.Cys310Tyr) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000064 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000011 ( 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: 4.54

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:

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=0.19959128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNG1A	NM_018491.5 link	c.929G>A	p.Cys310Tyr	missense_variant	Exon 13 of 15	ENST00000356521.9	NP_060961.3	Q9BRT8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNG1A	ENST00000356521.9 link	c.929G>A	p.Cys310Tyr	missense_variant	Exon 13 of 15	1	NM_018491.5	ENSP00000348915.4	Q9BRT8-1
ZNG1A	ENST00000465014.6 link	n.*527G>A		non_coding_transcript_exon_variant	Exon 13 of 15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 link	n.*650G>A		non_coding_transcript_exon_variant	Exon 14 of 16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000616944.4 link	n.*474G>A		non_coding_transcript_exon_variant	Exon 14 of 14	2		ENSP00000482821.1	A0A087WZQ3
ZNG1A	ENST00000619157.4 link	n.*474G>A		non_coding_transcript_exon_variant	Exon 10 of 12	5		ENSP00000483746.1	A0A087X0Y9
ZNG1A	ENST00000465014.6 link	n.*527G>A		3_prime_UTR_variant	Exon 13 of 15	2		ENSP00000482298.1	A0A087WTC0
ZNG1A	ENST00000612045.4 link	n.*650G>A		3_prime_UTR_variant	Exon 14 of 16	1		ENSP00000477749.1	A0A087WTC0
ZNG1A	ENST00000616944.4 link	n.*474G>A		3_prime_UTR_variant	Exon 14 of 14	2		ENSP00000482821.1	A0A087WZQ3
ZNG1A	ENST00000619157.4 link	n.*474G>A		3_prime_UTR_variant	Exon 10 of 12	5		ENSP00000483746.1	A0A087X0Y9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

125350

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000238

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000109

AC:

AN:

1371232

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

683582

show subpopulations

Gnomad4 AFR exome

AF:

0.000381

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:

9.53e-7

Gnomad4 OTH exome

AF:

0.0000348

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000638

AC:

AN:

125350

Hom.:

Cov.:

AF XY:

0.0000668

AC XY:

AN XY:

59908

show subpopulations

Gnomad4 AFR

AF:

0.000238

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:

0.000169

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.929G>A (p.C310Y) alteration is located in exon 13 (coding exon 13) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 929, causing the cysteine (C) at amino acid position 310 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.012

T;T;.;T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.84

.;T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;.;N;.;N

REVEL

Benign

0.16

Sift

Benign

0.15

T;.;T;.;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0010

B;B;B;.;B

Vest4

0.23

MutPred

0.50

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);.;.;.;

MVP

0.34

ClinPred

0.47

GERP RS

2.2

Varity_R

0.10

gMVP

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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