chr19-11722239-C-T

Variant names:

• chr19-11722239-C-T
• NM_001080493.4:c.1295G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.73
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05232528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080493.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF823	NM_001080493.4	MANE Select	c.1295G>A	p.Arg432Gln	missense	Exon 4 of 4	NP_001073962.1	P16415-1
	ZNF823	NM_017507.2		c.1163G>A	p.Arg388Gln	missense	Exon 3 of 3	NP_059977.1
	ZNF823	NM_001297610.2		c.749G>A	p.Arg250Gln	missense	Exon 3 of 3	NP_001284539.1	P16415-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF823	ENST00000341191.11	TSL:1 MANE Select	c.1295G>A	p.Arg432Gln	missense	Exon 4 of 4	ENSP00000340683.5	P16415-1
	ZNF823	ENST00000431998.1	TSL:1	c.1163G>A	p.Arg388Gln	missense	Exon 3 of 3	ENSP00000410654.1	C9J2N8
	ZNF823	ENST00000890454.1		c.1292G>A	p.Arg431Gln	missense	Exon 4 of 4	ENSP00000560513.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.3
DANN	Benign	0.70
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.000020	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.40	N
PhyloP100		-1.7
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.059
Sift	Benign	0.53	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	T
GERP RS		-1.1
Varity_R		0.048
gMVP		0.020
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr19-11833054; COSMIC: COSV57872512; COSMIC: COSV57872512;