16-3285113-G-T

Variant names:

• chr16-3285113-G-T
• rs140419803
• NM_005741.5:c.442G>T

Variant summary

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

The NM_005741.5(ZNF263):​c.442G>T​(p.Glu148*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF263 NM_005741.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.28
• Publications: 2 publications found

Genes affected

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located 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_005741.5. 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
	ZNF263	NM_005741.5	MANE Select	c.442G>T	p.Glu148*	stop_gained	Exon 2 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.442G>T	p.Glu148*	stop_gained	Exon 2 of 8	NP_001397944.1	D3DUC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	ENST00000219069.6	TSL:1 MANE Select	c.442G>T	p.Glu148*	stop_gained	Exon 2 of 6	ENSP00000219069.5	O14978
	ZNF263	ENST00000574674.2	TSL:2	c.442G>T	p.Glu148*	stop_gained	Exon 2 of 8	ENSP00000461755.2	D3DUC1
	ZNF263	ENST00000575332.2	TSL:3	c.442G>T	p.Glu148*	stop_gained	Exon 2 of 7	ENSP00000461146.2	D3DUC1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.86	D
PhyloP100		6.3
Vest4		0.28
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs140419803; hg19: chr16-3335113;