16-31435867-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136509.3(ZNF843):​c.983G>A​(p.Gly328Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000439 in 1,367,992 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

ZNF843
NM_001136509.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.351
Variant links:
Genes affected
ZNF843 (HGNC:28710): (zinc finger protein 843) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029577762).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF843NM_001136509.3 linkc.983G>A p.Gly328Glu missense_variant Exon 2 of 2 ENST00000315678.10 NP_001129981.1 Q8N446
ZNF843NM_001353381.1 linkc.983G>A p.Gly328Glu missense_variant Exon 2 of 2 NP_001340310.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF843ENST00000315678.10 linkc.983G>A p.Gly328Glu missense_variant Exon 2 of 2 2 NM_001136509.3 ENSP00000322899.5 Q8N446
ZNF843ENST00000618063.1 linkc.983G>A p.Gly328Glu missense_variant Exon 2 of 2 1 ENSP00000483573.1 Q8N446
ZNF843ENST00000564218.5 linkc.682+301G>A intron_variant Intron 2 of 2 5 ENSP00000455858.1 H3BQN5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
1
AN:
125484
Hom.:
0
AF XY:
0.0000149
AC XY:
1
AN XY:
66938
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000106
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
AF:
0.00000439
AC:
6
AN:
1367992
Hom.:
0
Cov.:
30
AF XY:
0.00000446
AC XY:
3
AN XY:
672318
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000849
Gnomad4 SAS exome
AF:
0.0000134
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000188
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.983G>A (p.G328E) alteration is located in exon 2 (coding exon 1) of the ZNF843 gene. This alteration results from a G to A substitution at nucleotide position 983, causing the glycine (G) at amino acid position 328 to be replaced by a glutamic acid (E). 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
0.44
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
15
DANN
Benign
0.73
DEOGEN2
Benign
0.00086
T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.00065
N
LIST_S2
Benign
0.35
.;T
M_CAP
Benign
0.0045
T
MetaRNN
Benign
0.030
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.25
N;.
REVEL
Benign
0.024
Sift
Pathogenic
0.0
D;.
Sift4G
Uncertain
0.059
T;T
Polyphen
0.013
B;B
Vest4
0.049
MutPred
0.27
Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP
0.072
ClinPred
0.065
T
GERP RS
-0.98
Varity_R
0.14
gMVP
0.011

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: rs1436466231; hg19: chr16-31447188; API