Genetic Variant ZNF582:p.Ile355Met (chr19-56384352-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320371.4(ZNF582):c.1065A>G(p.Ile355Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,610,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF582
NM_001320371.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.63

Publications

0 publications found

Variant links:

Genes affected

ZNF582 (HGNC:26421): (zinc finger protein 582) The protein encoded by this gene is a zing finger protein and putative transcription factor that is highly methylated in cervical cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ZNF582 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06974518).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320371.4. 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
	ZNF582	NM_001320371.4	MANE Select	c.1065A>G	p.Ile355Met	missense	Exon 5 of 5	NP_001307300.2	Q96NG8
	ZNF582	NM_144690.3		c.1065A>G	p.Ile355Met	missense	Exon 5 of 5	NP_653291.1	Q96NG8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF582	ENST00000586929.6	TSL:1 MANE Select	c.1065A>G	p.Ile355Met	missense	Exon 5 of 5	ENSP00000465619.1	Q96NG8
ZNF582	ENST00000301310.8	TSL:1	c.1065A>G	p.Ile355Met	missense	Exon 5 of 5	ENSP00000301310.3	Q96NG8
ZNF582	ENST00000932869.1		c.1065A>G	p.Ile355Met	missense	Exon 5 of 5	ENSP00000602928.1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149852

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000985

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000120

AC:

AN:

249918

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.00000479

AC:

AN:

1460826

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726718

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26030

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111566

Other (OTH)

AF:

0.00

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.0000267

AC:

AN:

149852

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73242

show subpopulations

African (AFR)

AF:

0.0000985

AC:

AN:

40624

American (AMR)

AF:

0.00

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5082

South Asian (SAS)

AF:

0.00

AC:

AN:

4666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67304

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

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

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.13

M_CAP

Benign

0.017

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

PhyloP100

-3.6

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.093

Sift

Uncertain

0.021

Sift4G

Uncertain

0.037

Polyphen

0.29

Vest4

0.20

MVP

0.088

MPC

0.41

ClinPred

0.17

GERP RS

-5.7

Varity_R

0.11

gMVP

0.037

Mutation Taster

=89/11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over