16-3283832-C-T

Variant names:

• chr16-3283832-C-T
• rs1005441851
• NM_005741.5:c.14C>T

Variant summary

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

The NM_005741.5(ZNF263):​c.14C>T​(p.Pro5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,422,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0590
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088867694).

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.14C>T	p.Pro5Leu	missense	Exon 1 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.14C>T	p.Pro5Leu	missense	Exon 1 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.14C>T	p.Pro5Leu	missense	Exon 1 of 6	ENSP00000219069.5	O14978
	ZNF263	ENST00000574674.2	TSL:2	c.14C>T	p.Pro5Leu	missense	Exon 1 of 8	ENSP00000461755.2	D3DUC1
	ZNF263	ENST00000575332.2	TSL:3	c.14C>T	p.Pro5Leu	missense	Exon 1 of 7	ENSP00000461146.2	D3DUC1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000449 AC: 1 AN: 222478 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000960

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1422778 Hom.: 0 Cov.: 30 AF XY: 0.00000283 AC XY: 2 AN XY: 706142

African (AFR) AF: 0.00 AC: 0 AN: 32250

American (AMR) AF: 0.00 AC: 0 AN: 39742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24282

East Asian (EAS) AF: 0.00 AC: 0 AN: 39026

South Asian (SAS) AF: 0.00 AC: 0 AN: 83198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4878

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095362

Other (OTH) AF: 0.00 AC: 0 AN: 58600

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.059
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.029
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.041	D
Polyphen		0.014	B
Vest4		0.27
MutPred		0.28		Loss of glycosylation at P5 (P = 0.0156)
MVP		0.14
MPC		0.23
ClinPred		0.23	T
GERP RS		3.1
PromoterAI		0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.47

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: rs1005441851; hg19: chr16-3333832;