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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF582	NM_001320371.4 link	c.1065A>G	p.Ile355Met	missense_variant	Exon 5 of 5	ENST00000586929.6	NP_001307300.2	Q96NG8
ZNF582	NM_144690.3 link	c.1065A>G	p.Ile355Met	missense_variant	Exon 5 of 5		NP_653291.1	Q96NG8A0A024R4P7
ZNF582	XR_007066621.1 link	n.1238A>G		non_coding_transcript_exon_variant	Exon 5 of 6
ZNF582	XR_430188.4 link	n.1460A>G		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF582	ENST00000586929.6 link	c.1065A>G	p.Ile355Met	missense_variant	Exon 5 of 5	1	NM_001320371.4	ENSP00000465619.1	Q96NG8
ZNF582	ENST00000301310.8 link	c.1065A>G	p.Ile355Met	missense_variant	Exon 5 of 5	1		ENSP00000301310.3	Q96NG8
ZNF582	ENST00000589143.5 link	c.232+5649A>G		intron_variant	Intron 4 of 4	5		ENSP00000468679.1	K7ESE7
ZNF582	ENST00000589895.2 link	c.232+5649A>G		intron_variant	Intron 4 of 4	2		ENSP00000465639.1	K7EKI7

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

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249918

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135060

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 SAS exome

AF:

0.0000658

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

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149852

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73242

show subpopulations

Gnomad4 AFR

AF:

0.0000985

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1065A>G (p.I355M) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a A to G substitution at nucleotide position 1065, causing the isoleucine (I) at amino acid position 355 to be replaced by a methionine (M). 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

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.13

.;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.30

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

N;.;.

REVEL

Benign

0.093

Sift

Uncertain

0.021

D;.;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.29

B;B;B

Vest4

0.20

MVP

0.088

MPC

0.41

ClinPred

0.17

GERP RS

-5.7

Varity_R

0.11

gMVP

0.037

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over