9-123412-C-T

Variant summary

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

The NM_018491.5(ZNG1A):​c.859G>A​(p.Glu287Lys) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 25)
Exomes 𝑓: 0.0000045 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNG1A
NM_018491.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNG1ANM_018491.5 linkc.859G>A p.Glu287Lys missense_variant Exon 12 of 15 ENST00000356521.9 NP_060961.3 Q9BRT8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNG1AENST00000356521.9 linkc.859G>A p.Glu287Lys missense_variant Exon 12 of 15 1 NM_018491.5 ENSP00000348915.4 Q9BRT8-1
ZNG1AENST00000465014.6 linkn.*457G>A non_coding_transcript_exon_variant Exon 12 of 15 2 ENSP00000482298.1 A0A087WTC0
ZNG1AENST00000612045.4 linkn.*580G>A non_coding_transcript_exon_variant Exon 13 of 16 1 ENSP00000477749.1 A0A087WTC0
ZNG1AENST00000616944.4 linkn.*404G>A non_coding_transcript_exon_variant Exon 13 of 14 2 ENSP00000482821.1 A0A087WZQ3
ZNG1AENST00000619157.4 linkn.*404G>A non_coding_transcript_exon_variant Exon 9 of 12 5 ENSP00000483746.1 A0A087X0Y9
ZNG1AENST00000465014.6 linkn.*457G>A 3_prime_UTR_variant Exon 12 of 15 2 ENSP00000482298.1 A0A087WTC0
ZNG1AENST00000612045.4 linkn.*580G>A 3_prime_UTR_variant Exon 13 of 16 1 ENSP00000477749.1 A0A087WTC0
ZNG1AENST00000616944.4 linkn.*404G>A 3_prime_UTR_variant Exon 13 of 14 2 ENSP00000482821.1 A0A087WZQ3
ZNG1AENST00000619157.4 linkn.*404G>A 3_prime_UTR_variant Exon 9 of 12 5 ENSP00000483746.1 A0A087X0Y9

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
150606
Hom.:
0
Cov.:
25
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000662
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000454
AC:
6
AN:
1322362
Hom.:
0
Cov.:
23
AF XY:
0.00000755
AC XY:
5
AN XY:
662638
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000797
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:
0.00000295
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000133
AC:
2
AN:
150606
Hom.:
0
Cov.:
25
AF XY:
0.0000272
AC XY:
2
AN XY:
73416
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000662
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.859G>A (p.E287K) alteration is located in exon 12 (coding exon 12) of the CBWD1 gene. This alteration results from a G to A substitution at nucleotide position 859, causing the glutamic acid (E) at amino acid position 287 to be replaced by a lysine (K). 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
0.16
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0094
T;T;.;T;.
Eigen
Benign
-0.070
Eigen_PC
Benign
-0.022
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
.;D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;M;.;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-0.98
N;.;N;.;N
REVEL
Benign
0.22
Sift
Benign
0.26
T;.;T;.;T
Sift4G
Benign
0.64
T;T;T;T;T
Polyphen
0.12
B;B;B;.;B
Vest4
0.63
MutPred
0.51
Gain of helix (P = 0.0093);Gain of helix (P = 0.0093);.;.;.;
MVP
0.75
ClinPred
0.24
T
GERP RS
3.2
Varity_R
0.36
gMVP
0.041

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.

Other links and lift over

dbSNP: rs1405584714; hg19: chr9-123412; API