16-3290106-G-A

Variant names:

• chr16-3290106-G-A
• rs34236132
• NM_005741.5:c.1600G>A

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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 0.0045 (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
• Publications: 8 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005741.5. 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.1600G>A	p.Val534Ile	missense	Exon 6 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.1600G>A	p.Val534Ile	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.1600G>A	p.Val534Ile	missense	Exon 6 of 6	ENSP00000219069.5
	ZNF263	ENST00000574674.2	TSL:2	c.1600G>A	p.Val534Ile	missense	Exon 6 of 8	ENSP00000461755.2
	ZNF263	ENST00000575332.2	TSL:3	c.1600G>A	p.Val534Ile	missense	Exon 6 of 7	ENSP00000461146.2

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

GnomAD2 exomes AF: 0.00150 AC: 377 AN: 251360 AF XY: 0.00121

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 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

African (AFR) AF: 0.0133 AC: 446 AN: 33480

American (AMR) AF: 0.00186 AC: 83 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 29 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.000556 AC: 618 AN: 1112004

Other (OTH) AF: 0.00146 AC: 88 AN: 60396

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

African (AFR) AF: 0.0143 AC: 590 AN: 41380

American (AMR) AF: 0.00275 AC: 42 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.000516 AC: 35 AN: 67878

Other (OTH) AF: 0.00523 AC: 11 AN: 2104

Alfa AF: 0.00206 Hom.: 3

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 v4.9

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
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.00021	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.19
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.018	B
Vest4		0.027
MVP		0.048
MPC		0.57
ClinPred		0.017	T
GERP RS		4.8
PromoterAI		-0.0032	Neutral
Varity_R		0.041
gMVP		0.079
Mutation Taster		=100/0	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: rs34236132; hg19: chr16-3340106;