chr16-3289435-G-C

Variant names:

• chr16-3289435-G-C
• rs220379
• NM_005741.5:c.929G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000219069.6(ZNF263):​c.929G>C​(p.Cys310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,523,816 control chromosomes in the GnomAD database, including 51,989 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (9402 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42587 hom.)
• Consequence: ZNF263 ENST00000219069.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 41 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.514655E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000219069.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	NM_005741.5	MANE Select	c.929G>C	p.Cys310Ser	missense	Exon 6 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.929G>C	p.Cys310Ser	missense	Exon 6 of 8	NP_001397944.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	ENST00000219069.6	TSL:1 MANE Select	c.929G>C	p.Cys310Ser	missense	Exon 6 of 6	ENSP00000219069.5
	ZNF263	ENST00000574674.2	TSL:2	c.929G>C	p.Cys310Ser	missense	Exon 6 of 8	ENSP00000461755.2
	ZNF263	ENST00000575332.2	TSL:3	c.929G>C	p.Cys310Ser	missense	Exon 6 of 7	ENSP00000461146.2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48809 AN: 151892 Hom.: 9377 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.262 AC: 46818 AN: 178864 AF XY: 0.249

Gnomad AFR exome AF: 0.523

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.0428

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.240 AC: 329100 AN: 1371806 Hom.: 42587 Cov.: 33 AF XY: 0.235 AC XY: 158530 AN XY: 673310

African (AFR) AF: 0.517 AC: 15666 AN: 30310

American (AMR) AF: 0.359 AC: 10495 AN: 29250

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 4719 AN: 19990

East Asian (EAS) AF: 0.0386 AC: 1508 AN: 39048

South Asian (SAS) AF: 0.116 AC: 8159 AN: 70586

European-Finnish (FIN) AF: 0.286 AC: 14275 AN: 49938

Middle Eastern (MID) AF: 0.152 AC: 808 AN: 5320

European-Non Finnish (NFE) AF: 0.243 AC: 260113 AN: 1070918

Other (OTH) AF: 0.237 AC: 13357 AN: 56446

GnomAD4 genome AF: 0.322 AC: 48876 AN: 152010 Hom.: 9402 Cov.: 32 AF XY: 0.319 AC XY: 23706 AN XY: 74292

African (AFR) AF: 0.517 AC: 21395 AN: 41422

American (AMR) AF: 0.338 AC: 5162 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3466

East Asian (EAS) AF: 0.0395 AC: 204 AN: 5164

South Asian (SAS) AF: 0.109 AC: 528 AN: 4822

European-Finnish (FIN) AF: 0.285 AC: 3013 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16872 AN: 67966

Other (OTH) AF: 0.300 AC: 633 AN: 2110

Alfa AF: 0.229 Hom.: 2463

Bravo AF: 0.338

TwinsUK AF: 0.232 AC: 860

ALSPAC AF: 0.227 AC: 876

ESP6500AA AF: 0.514 AC: 2258

ESP6500EA AF: 0.245 AC: 2111

ExAC AF: 0.253 AC: 29825

Asia WGS AF: 0.105 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.92
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000085	T
PhyloP100		-1.2
Sift4G	Benign	0.52	T
Vest4		0.031
ClinPred		0.0052	T
GERP RS		-0.92
Varity_R		0.029
Mutation Taster		=100/0	polymorphism (auto)

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: rs220379; hg19: chr16-3339435; COSMIC: COSV54595286; COSMIC: COSV54595286;