Genetic Variant ZNF823:p.Arg432Gln (chr19-11722239-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_001080493.4(ZNF823):c.1295G>A(p.Arg432Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF823
NM_001080493.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

ZNF823 (HGNC:30936): (zinc finger protein 823) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF823 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=0.05232528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF823	NM_001080493.4 link	c.1295G>A	p.Arg432Gln	missense_variant	Exon 4 of 4	ENST00000341191.11	NP_001073962.1	P16415-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF823	ENST00000341191.11 link	c.1295G>A	p.Arg432Gln	missense_variant	Exon 4 of 4	1	NM_001080493.4	ENSP00000340683.5		P16415-1
ZNF823	ENST00000431998.1 link	c.1163G>A	p.Arg388Gln	missense_variant	Exon 3 of 3	1		ENSP00000410654.1		C9J2N8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

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

Feb 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1295G>A (p.R432Q) alteration is located in exon 4 (coding exon 4) of the ZNF823 gene. This alteration results from a G to A substitution at nucleotide position 1295, causing the arginine (R) at amino acid position 432 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.3

DANN

Benign

0.70

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.000020

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.40

N;.

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.3

N;D

REVEL

Benign

0.059

Sift

Benign

0.53

T;T

Sift4G

Benign

0.51

T;.

Polyphen

0.73

P;.

Vest4

0.026

MutPred

0.42

Loss of catalytic residue at R432 (P = 0.0343);.;

MVP

0.12

MPC

0.49

ClinPred

0.10

GERP RS

-1.1

Varity_R

0.048

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over