Genetic Variant ZNF653:p.Arg566Gln (chr19-11483833-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138783.4(ZNF653):c.1697G>A(p.Arg566Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,422,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF653
NM_138783.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Publications

0 publications found

Variant links:

Genes affected

ZNF653 (HGNC:25196): (zinc finger protein 653) Enables AF-2 domain binding activity and transcription corepressor activity. Involved in extracellular negative regulation of signal transduction and negative regulation of nucleic acid-templated transcription. Predicted to be located in extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF653 links:

ENSG00000267477 (HGNC:):

ENSG00000267477 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138783.4. 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
	ZNF653	NM_138783.4	MANE Select	c.1697G>A	p.Arg566Gln	missense	Exon 9 of 9	NP_620138.2	Q96CK0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF653	ENST00000293771.10	TSL:1 MANE Select	c.1697G>A	p.Arg566Gln	missense	Exon 9 of 9	ENSP00000293771.3	Q96CK0
ENSG00000267477	ENST00000585656.1	TSL:5	n.469+12117G>A		intron	N/A	ENSP00000466387.1	K7EM74
ZNF653	ENST00000937056.1		c.1085G>A	p.Arg362Gln	missense	Exon 8 of 8	ENSP00000607115.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

234666

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000141

AC:

AN:

1422028

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32488

American (AMR)

AF:

0.0000234

AC:

AN:

42692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24784

East Asian (EAS)

AF:

0.00

AC:

AN:

37110

South Asian (SAS)

AF:

0.00

AC:

AN:

84978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088860

Other (OTH)

AF:

0.0000173

AC:

AN:

57874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

5.9

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.25

Sift

Uncertain

0.020

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.67

MutPred

0.48

Loss of MoRF binding (P = 0.0464)

MVP

0.58

MPC

1.9

ClinPred

1.0

GERP RS

4.1

Varity_R

0.62

gMVP

0.53

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over