Genetic Variant ZNF843:p.Ser322Trp (chr16-31435885-G-C) – 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.965C>G(p.Ser322Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,540,386 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

ZNF843
NM_001136509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.49

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:

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=0.018449157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF843	NM_001136509.3 link	c.965C>G	p.Ser322Trp	missense_variant	Exon 2 of 2	ENST00000315678.10	NP_001129981.1	Q8N446
ZNF843	NM_001353381.1 link	c.965C>G	p.Ser322Trp	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.965C>G	p.Ser322Trp	missense_variant	Exon 2 of 2	2	NM_001136509.3	ENSP00000322899.5	Q8N446
ZNF843	ENST00000618063.1 link	c.965C>G	p.Ser322Trp	missense_variant	Exon 2 of 2	1		ENSP00000483573.1	Q8N446
ZNF843	ENST00000564218.5 link	c.682+283C>G		intron_variant	Intron 2 of 2	5		ENSP00000455858.1	H3BQN5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

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

GnomAD3 exomes

AF:

0.0000424

AC:

AN:

141546

Hom.:

AF XY:

0.0000264

AC XY:

AN XY:

75760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000586

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:

0.00000792

AC:

AN:

1388040

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

683870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000584

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000225

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.965C>G (p.S322W) alteration is located in exon 2 (coding exon 1) of the ZNF843 gene. This alteration results from a C to G substitution at nucleotide position 965, causing the serine (S) at amino acid position 322 to be replaced by a tryptophan (W). 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

0.34

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.0014

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.018

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.31

N;.

REVEL

Benign

0.017

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.015

D;D

Polyphen

0.0060

B;B

Vest4

0.21

MutPred

0.21

Loss of glycosylation at S322 (P = 0.009);Loss of glycosylation at S322 (P = 0.009);

MVP

0.081

ClinPred

0.030

GERP RS

-2.6

Varity_R

0.073

gMVP

0.020

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