19-11722051-C-T

Variant names:

• chr19-11722051-C-T
• NM_001080493.4:c.1483G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080493.4(ZNF823):​c.1483G>A​(p.Val495Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: ZNF823 NM_001080493.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.48
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089716166).

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.1483G>A	p.Val495Ile	missense	Exon 4 of 4	NP_001073962.1	P16415-1
	ZNF823	NM_017507.2		c.1351G>A	p.Val451Ile	missense	Exon 3 of 3	NP_059977.1
	ZNF823	NM_001297610.2		c.937G>A	p.Val313Ile	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.1483G>A	p.Val495Ile	missense	Exon 4 of 4	ENSP00000340683.5	P16415-1
	ZNF823	ENST00000431998.1	TSL:1	c.1351G>A	p.Val451Ile	missense	Exon 3 of 3	ENSP00000410654.1	C9J2N8
	ZNF823	ENST00000890454.1		c.1480G>A	p.Val494Ile	missense	Exon 4 of 4	ENSP00000560513.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.098
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.97
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.00097	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		2.5
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.36	B
Vest4		0.084
MutPred		0.35		Loss of ubiquitination at K490 (P = 0.1576)
MVP		0.30
MPC		0.43
ClinPred		0.40	T
GERP RS		0.48
Varity_R		0.078
gMVP		0.012
Mutation Taster		=91/9	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: chr19-11832866;