rs34236132

Positions:

• chr16-3290106-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005741.5(ZNF263):​c.1600G>A​(p.Val534Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,590 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.0045 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00088 (3 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038508475).
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF263	NM_005741.5	c.1600G>A	p.Val534Ile	missense_variant	6/6	ENST00000219069.6
ZNF263	NM_001411015.1	c.1600G>A	p.Val534Ile	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF263	ENST00000219069.6	c.1600G>A	p.Val534Ile	missense_variant	6/6	1	NM_005741.5	P4
	ENST00000703449.1	c.544G>A	p.Val182Ile	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes AF: 0.00449 AC: 681 AN: 151602 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.000516

Gnomad OTH AF: 0.00528

GnomAD3 exomes AF: 0.00150 AC: 377 AN: 251360 Hom.: 2 AF XY: 0.00121 AC XY: 164 AN XY: 135876

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000554

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000876 AC: 1280 AN: 1461870 Hom.: 3 Cov.: 32 AF XY: 0.000784 AC XY: 570 AN XY: 727232

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000556

Gnomad4 OTH exome AF: 0.00146

GnomAD4 genome AF: 0.00450 AC: 682 AN: 151720 Hom.: 7 Cov.: 32 AF XY: 0.00418 AC XY: 310 AN XY: 74132

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000516

Gnomad4 OTH AF: 0.00523

Alfa AF: 0.00128 Hom.: 2

Bravo AF: 0.00520

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0184 AC: 81

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00170 AC: 207

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.0051	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.54	T;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.020	N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.018	.;B
Vest4		0.027
MVP		0.048
MPC		0.57
ClinPred		0.017	T
GERP RS		4.8
Varity_R		0.041
gMVP		0.079

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: rs34236132; hg19: chr16-3340106;