16-3283826-C-T

Position:

• chr16-3283826-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005741.5(ZNF263):​c.8C>T​(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,415,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.000014 (0 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.863

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]

ENSG00000290183 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06808066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF263	NM_005741.5	c.8C>T	p.Ser3Leu	missense_variant	1/6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1	c.8C>T	p.Ser3Leu	missense_variant	1/8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6	c.8C>T	p.Ser3Leu	missense_variant	1/6	1	NM_005741.5	ENSP00000219069.5
ENSG00000290183	ENST00000703449.1	c.-170-5567C>T		intron_variant				ENSP00000515300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000141 AC: 20 AN: 1415126 Hom.: 0 Cov.: 30 AF XY: 0.0000128 AC XY: 9 AN XY: 701956

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000183

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2023

The c.8C>T (p.S3L) alteration is located in exon 1 (coding exon 1) of the ZNF263 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a leucine (L). 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	Benign	0.18
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.;T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.068	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.56	N;.;.;.
REVEL	Benign	0.045
Sift	Benign	0.14	T;.;.;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.38	B;.;.;.
Vest4		0.11
MutPred		0.26		Loss of glycosylation at S3 (P = 0.0073);Loss of glycosylation at S3 (P = 0.0073);Loss of glycosylation at S3 (P = 0.0073);Loss of glycosylation at S3 (P = 0.0073);
MVP		0.16
MPC		0.16
ClinPred		0.17	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.36

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: chr16-3333826;