16-3285165-G-A

Position:

• chr16-3285165-G-A

Variant summary

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

The NM_005741.5(ZNF263):​c.494G>A​(p.Arg165Gln) 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. 13/21 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)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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=0.09572178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF263	NM_005741.5	c.494G>A	p.Arg165Gln	missense_variant	2/6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1	c.494G>A	p.Arg165Gln	missense_variant	2/8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6	c.494G>A	p.Arg165Gln	missense_variant	2/6	1	NM_005741.5	ENSP00000219069.5
ENSG00000290183	ENST00000703449.1	c.-170-4228G>A		intron_variant				ENSP00000515300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 27, 2023

The c.494G>A (p.R165Q) alteration is located in exon 2 (coding exon 2) of the ZNF263 gene. This alteration results from a G to A substitution at nucleotide position 494, causing the arginine (R) at amino acid position 165 to be replaced by a glutamine (Q). 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	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.015
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.14	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.062
Sift	Benign	0.58	T
Sift4G	Benign	0.70	T
Polyphen		0.82	P
Vest4		0.22
MutPred		0.22		Gain of relative solvent accessibility (P = 0.0507);
MVP		0.26
MPC		0.79
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.075
gMVP		0.26

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: chr16-3335165;