16-3285113-G-A

Variant names:

• chr16-3285113-G-A
• rs140419803
• NM_005741.5:c.442G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005741.5(ZNF263):​c.442G>A​(p.Glu148Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000354 in 1,614,162 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: ZNF263 NM_005741.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.28
• Publications: 2 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.106869936).
• BS2: High Homozygotes in GnomAdExome4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	NM_005741.5	MANE Select	c.442G>A	p.Glu148Lys	missense	Exon 2 of 6	NP_005732.2
	ZNF263	NM_001411015.1		c.442G>A	p.Glu148Lys	missense	Exon 2 of 8	NP_001397944.1	D3DUC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	ENST00000219069.6	TSL:1 MANE Select	c.442G>A	p.Glu148Lys	missense	Exon 2 of 6	ENSP00000219069.5	O14978
	ZNF263	ENST00000574674.2	TSL:2	c.442G>A	p.Glu148Lys	missense	Exon 2 of 8	ENSP00000461755.2	D3DUC1
	ZNF263	ENST00000575332.2	TSL:3	c.442G>A	p.Glu148Lys	missense	Exon 2 of 7	ENSP00000461146.2	D3DUC1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000219 AC: 55 AN: 251448 AF XY: 0.000243

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000361 AC: 528 AN: 1461846 Hom.: 2 Cov.: 31 AF XY: 0.000360 AC XY: 262 AN XY: 727222

African (AFR) AF: 0.000119 AC: 4 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53416

Middle Eastern (MID) AF: 0.000697 AC: 4 AN: 5740

European-Non Finnish (NFE) AF: 0.000432 AC: 480 AN: 1112008

Other (OTH) AF: 0.000431 AC: 26 AN: 60394

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74468

African (AFR) AF: 0.0000721 AC: 3 AN: 41582

American (AMR) AF: 0.000261 AC: 4 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000514 AC: 35 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000352 Hom.: 0

Bravo AF: 0.000332

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000239 AC: 29

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.074	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.46	N
PhyloP100		6.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.086
Sift	Benign	0.35	T
Sift4G	Benign	0.20	T
Polyphen		0.98	D
Vest4		0.45
MVP		0.26
MPC		0.35
ClinPred		0.045	T
GERP RS		3.8
Varity_R		0.17
gMVP		0.48
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140419803; hg19: chr16-3335113;