19-11722270-C-A

Variant names:

• chr19-11722270-C-A
• NM_001080493.4:c.1264G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080493.4(ZNF823):​c.1264G>T​(p.Gly422Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF823 NM_001080493.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF823	NM_001080493.4	c.1264G>T	p.Gly422Cys	missense_variant	Exon 4 of 4	ENST00000341191.11	NP_001073962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF823	ENST00000341191.11	c.1264G>T	p.Gly422Cys	missense_variant	Exon 4 of 4	1	NM_001080493.4	ENSP00000340683.5
ZNF823	ENST00000431998.1	c.1132G>T	p.Gly378Cys	missense_variant	Exon 3 of 3	1		ENSP00000410654.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1264G>T (p.G422C) alteration is located in exon 4 (coding exon 4) of the ZNF823 gene. This alteration results from a G to T substitution at nucleotide position 1264, causing the glycine (G) at amino acid position 422 to be replaced by a cysteine (C). 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	0.56
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	0.071
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0011	T
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.25
MutPred		0.67		Gain of methylation at K423 (P = 0.0753);.;
MVP		0.57
MPC		1.3
ClinPred		0.98	D
GERP RS		0.57
Varity_R		0.64
gMVP		0.039

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.

Other links and lift over

hg19: chr19-11833085;