rs756608770

Variant names:

• chr19-11721775-C-A
• rs756608770
• NM_001080493.4:c.1759G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-11721775-C-A
• chr19-11721775-C-T

Variant summary

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

The NM_001080493.4(ZNF823):​c.1759G>T​(p.Glu587*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF823 NM_001080493.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• 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 2 ACMG points.

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

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.1759G>T	p.Glu587*	stop_gained	Exon 4 of 4	NP_001073962.1	P16415-1
	ZNF823	NM_017507.2		c.1627G>T	p.Glu543*	stop_gained	Exon 3 of 3	NP_059977.1
	ZNF823	NM_001297610.2		c.1213G>T	p.Glu405*	stop_gained	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.1759G>T	p.Glu587*	stop_gained	Exon 4 of 4	ENSP00000340683.5	P16415-1
	ZNF823	ENST00000890454.1		c.1756G>T	p.Glu586*	stop_gained	Exon 4 of 4	ENSP00000560513.1
	ZNF823	ENST00000431998.1	TSL:1	c.*218G>T		downstream_gene	N/A	ENSP00000410654.1	C9J2N8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	32
DANN	Uncertain	0.98
Eigen	Benign	-0.060
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.00065	N
PhyloP100		-0.29
Vest4		0.019
GERP RS		-0.74
Mutation Taster		=162/38	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

dbSNP: rs756608770; hg19: chr19-11832590;