Genetic Variant ZNF843:p.Gly328Glu (chr16-31435867-C-T) – ACMG Classification: Likely_benign (-2 pts)

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

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]

ZNF843 links:

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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
ZNF843	NM_001136509.3 link	c.983G>A	p.Gly328Glu	missense_variant	Exon 2 of 2	ENST00000315678.10	NP_001129981.1	Q8N446
ZNF843	NM_001353381.1 link	c.983G>A	p.Gly328Glu	missense_variant	Exon 2 of 2		NP_001340310.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF843	ENST00000315678.10 link	c.983G>A	p.Gly328Glu	missense_variant	Exon 2 of 2	2	NM_001136509.3	ENSP00000322899.5	Q8N446
ZNF843	ENST00000618063.1 link	c.983G>A	p.Gly328Glu	missense_variant	Exon 2 of 2	1		ENSP00000483573.1	Q8N446
ZNF843	ENST00000564218.5 link	c.682+301G>A		intron_variant	Intron 2 of 2	5		ENSP00000455858.1	H3BQN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

125484

Hom.:

AF XY:

0.0000149

AC XY:

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:

AN:

1367992

Hom.:

Cov.:

AF XY:

0.00000446

AC XY:

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.:

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

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.00086

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.35

.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.030

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.49

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

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.

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