Variant chr19-56383978-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320371.4(ZNF582):c.1439A>G(p.Asn480Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF582
NM_001320371.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0470

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=0.087546766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF582	NM_001320371.4 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	5/5	ENST00000586929.6	NP_001307300.2
ZNF582	NM_144690.3 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	5/5		NP_653291.1
ZNF582	XR_007066621.1 linkuse as main transcript	n.1612A>G		non_coding_transcript_exon_variant	5/6
ZNF582	XR_430188.4 linkuse as main transcript	n.1834A>G		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF582	ENST00000586929.6 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	5/5	1	NM_001320371.4	ENSP00000465619	P1
ZNF582	ENST00000301310.8 linkuse as main transcript	c.1439A>G	p.Asn480Ser	missense_variant	5/5	1		ENSP00000301310	P1
ZNF582	ENST00000589143.5 linkuse as main transcript	c.232+6023A>G		intron_variant		5		ENSP00000468679
ZNF582	ENST00000589895.2 linkuse as main transcript	c.232+6023A>G		intron_variant		2		ENSP00000465639

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251114

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461644

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The c.1439A>G (p.N480S) 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 1439, causing the asparagine (N) at amino acid position 480 to be replaced by a serine (S). 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

0.084

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.15

.;T;.

M_CAP

Benign

0.0027

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.15

N;N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.020

N;.;.

REVEL

Benign

0.037

Sift

Benign

0.18

T;.;.

Sift4G

Benign

0.37

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.070

MutPred

0.39

Gain of disorder (P = 0.0815);Gain of disorder (P = 0.0815);Gain of disorder (P = 0.0815);

MVP

0.12

MPC

0.10

ClinPred

0.040

GERP RS

2.0

Varity_R

0.036

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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