rs114652786

Variant names:

• chr9-111527720-A-G
• rs114652786
• NM_133464.5:c.325A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_133464.5(ZNF483):​c.325A>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,180 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03340912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF483	NM_133464.5	c.325A>G	p.Arg109Gly	missense_variant	Exon 2 of 6	ENST00000309235.6	NP_597721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF483	ENST00000309235.6	c.325A>G	p.Arg109Gly	missense_variant	Exon 2 of 6	1	NM_133464.5	ENSP00000311679.5
ZNF483	ENST00000355824.7	c.325A>G	p.Arg109Gly	missense_variant	Exon 2 of 6	1		ENSP00000438048.1
ZNF483	ENST00000358151.8	c.325A>G	p.Arg109Gly	missense_variant	Exon 2 of 6	2		ENSP00000350871.4
ZNF483	ENST00000374374.3	c.325A>G	p.Arg109Gly	missense_variant	Exon 2 of 2	2		ENSP00000363494.3

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152214 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251308 AF XY: 0.0000957

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 52 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23 AN XY: 727222

African (AFR) AF: 0.00119 AC: 40 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.000132 AC: 8 AN: 60392

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152332 Hom.: 1 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74498

African (AFR) AF: 0.000914 AC: 38 AN: 41584

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

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

Alfa AF: 0.000656 Hom.: 0

Bravo AF: 0.000491

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325A>G (p.R109G) alteration is located in exon 2 (coding exon 1) of the ZNF483 gene. This alteration results from a A to G substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	.;T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.033	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;.;.;M
PhyloP100		1.2
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-6.6	D;D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.98, 1.0, 0.97	.;D;D;D
Vest4		0.26
MVP		0.43
MPC		0.95
ClinPred		0.20	T
GERP RS		4.3
Varity_R		0.34
gMVP		0.52
Mutation Taster		=60/40	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: rs114652786; hg19: chr9-114290000;