chr19-56384038-A-G

Variant summary

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

The NM_001320371.4(ZNF582):ā€‹c.1379T>Cā€‹(p.Leu460Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

ZNF582
NM_001320371.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.24
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]

Genome browser will be placed here

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=0.1809032).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF582NM_001320371.4 linkuse as main transcriptc.1379T>C p.Leu460Ser missense_variant 5/5 ENST00000586929.6 NP_001307300.2
ZNF582NM_144690.3 linkuse as main transcriptc.1379T>C p.Leu460Ser missense_variant 5/5 NP_653291.1
ZNF582XR_007066621.1 linkuse as main transcriptn.1552T>C non_coding_transcript_exon_variant 5/6
ZNF582XR_430188.4 linkuse as main transcriptn.1774T>C non_coding_transcript_exon_variant 5/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF582ENST00000586929.6 linkuse as main transcriptc.1379T>C p.Leu460Ser missense_variant 5/51 NM_001320371.4 ENSP00000465619 P1
ZNF582ENST00000301310.8 linkuse as main transcriptc.1379T>C p.Leu460Ser missense_variant 5/51 ENSP00000301310 P1
ZNF582ENST00000589143.5 linkuse as main transcriptc.232+5963T>C intron_variant 5 ENSP00000468679
ZNF582ENST00000589895.2 linkuse as main transcriptc.232+5963T>C intron_variant 2 ENSP00000465639

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
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
GnomAD4 exome
AF:
0.00000548
AC:
8
AN:
1460848
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726684
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

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 submitterclinical testingAmbry GeneticsFeb 28, 2023The c.1379T>C (p.L460S) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a T to C substitution at nucleotide position 1379, causing the leucine (L) at amino acid position 460 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
0.080
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.062
T;T;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.56
.;T;.
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.82
L;L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.6
N;.;.
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D;.;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.48
P;P;P
Vest4
0.17
MutPred
0.62
Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);Loss of stability (P = 0.0211);
MVP
0.42
MPC
0.28
ClinPred
0.35
T
GERP RS
2.4
Varity_R
0.13
gMVP
0.21

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.

Other links and lift over

dbSNP: rs955097380; hg19: chr19-56895407; API