16-3289435-G-C

Position:

• chr16-3289435-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005741.5(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. 10/14 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.32 (9402 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42587 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF263	NM_005741.5	c.929G>C	p.Cys310Ser	missense_variant	6/6	ENST00000219069.6
ZNF263	NM_001411015.1	c.929G>C	p.Cys310Ser	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF263	ENST00000219069.6	c.929G>C	p.Cys310Ser	missense_variant	6/6	1	NM_005741.5	P4
	ENST00000703449.1	c.-128G>C		5_prime_UTR_variant	2/2			P1

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

GnomAD3 exomes AF: 0.262 AC: 46818 AN: 178864 Hom.: 7322 AF XY: 0.249 AC XY: 23433 AN XY: 93966

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 SAS exome AF: 0.110

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

Gnomad4 AFR exome AF: 0.517

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0386

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.237

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

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.300

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 v4.3

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
MutationTaster	Benign	1.0	P;P;P
Sift4G	Benign	0.52	T
Vest4		0.031
ClinPred		0.0052	T
GERP RS		-0.92

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

LitVar

Other links and lift over

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