16-3283829-G-T

Variant names:

• chr16-3283829-G-T
• rs888383569
• NM_005741.5:c.11G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005741.5(ZNF263):​c.11G>T​(p.Gly4Val) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06553474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF263	NM_005741.5	c.11G>T	p.Gly4Val	missense_variant	Exon 1 of 6	ENST00000219069.6	NP_005732.2
ZNF263	NM_001411015.1	c.11G>T	p.Gly4Val	missense_variant	Exon 1 of 8		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF263	ENST00000219069.6	c.11G>T	p.Gly4Val	missense_variant	Exon 1 of 6	1	NM_005741.5	ENSP00000219069.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 221854 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000141 AC: 2 AN: 1421204 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 705322

African (AFR) AF: 0.00 AC: 0 AN: 32286

American (AMR) AF: 0.00 AC: 0 AN: 39732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39014

South Asian (SAS) AF: 0.00 AC: 0 AN: 82994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4768

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1094774

Other (OTH) AF: 0.00 AC: 0 AN: 58568

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00097	N
LIST_S2	Benign	0.59	T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.28	N;.;.;.
PhyloP100		-0.26
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.1	N;.;.;.
REVEL	Benign	0.043
Sift	Benign	0.11	T;.;.;.
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.11
MutPred		0.25		Loss of glycosylation at S3 (P = 0.0238);Loss of glycosylation at S3 (P = 0.0238);Loss of glycosylation at S3 (P = 0.0238);Loss of glycosylation at S3 (P = 0.0238);
MVP		0.16
MPC		0.24
ClinPred		0.050	T
GERP RS		-3.3
PromoterAI		-0.061	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.27
Mutation Taster		=90/10	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: rs888383569; hg19: chr16-3333829;