Genetic Variant ZNF843:p.Ala242Thr (chr16-31436126-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.724G>A(p.Ala242Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,549,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ZNF843
NM_001136509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0890

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=0.05441618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF843	NM_001136509.3 link	c.724G>A	p.Ala242Thr	missense_variant	Exon 2 of 2	ENST00000315678.10	NP_001129981.1	Q8N446
ZNF843	NM_001353381.1 link	c.724G>A	p.Ala242Thr	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.724G>A	p.Ala242Thr	missense_variant	Exon 2 of 2	2	NM_001136509.3	ENSP00000322899.5	Q8N446
ZNF843	ENST00000618063.1 link	c.724G>A	p.Ala242Thr	missense_variant	Exon 2 of 2	1		ENSP00000483573.1	Q8N446
ZNF843	ENST00000564218.5 link	c.682+42G>A		intron_variant	Intron 2 of 2	5		ENSP00000455858.1	H3BQN5

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000114

AC:

AN:

149310

Hom.:

AF XY:

0.000139

AC XY:

AN XY:

79222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000574

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000529

AC:

AN:

1397554

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

689200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000536

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:

0.0000482

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.000131

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000774

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.0000345

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.724G>A (p.A242T) 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 724, causing the alanine (A) at amino acid position 242 to be replaced by a threonine (T). 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

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0017

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.063

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.94

P;P

Vest4

0.042

MutPred

0.18

Gain of glycosylation at A242 (P = 0.0034);Gain of glycosylation at A242 (P = 0.0034);

MVP

0.030

ClinPred

0.083

GERP RS

-2.1

Varity_R

0.071

gMVP

0.085

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