chr19-56384081-T-C

Variant summary

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

The NM_001320371.4(ZNF582):ā€‹c.1336A>Gā€‹(p.Thr446Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,610,916 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

ZNF582
NM_001320371.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.684
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=0.077385366).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF582NM_001320371.4 linkuse as main transcriptc.1336A>G p.Thr446Ala missense_variant 5/5 ENST00000586929.6 NP_001307300.2
ZNF582NM_144690.3 linkuse as main transcriptc.1336A>G p.Thr446Ala missense_variant 5/5 NP_653291.1
ZNF582XR_007066621.1 linkuse as main transcriptn.1509A>G non_coding_transcript_exon_variant 5/6
ZNF582XR_430188.4 linkuse as main transcriptn.1731A>G 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.1336A>G p.Thr446Ala missense_variant 5/51 NM_001320371.4 ENSP00000465619 P1
ZNF582ENST00000301310.8 linkuse as main transcriptc.1336A>G p.Thr446Ala missense_variant 5/51 ENSP00000301310 P1
ZNF582ENST00000589143.5 linkuse as main transcriptc.232+5920A>G intron_variant 5 ENSP00000468679
ZNF582ENST00000589895.2 linkuse as main transcriptc.232+5920A>G intron_variant 2 ENSP00000465639

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152254
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
247828
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
133954
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000468
Gnomad NFE exome
AF:
0.0000445
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1458662
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
725622
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152254
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsApr 01, 2024The c.1336A>G (p.T446A) 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 1336, causing the threonine (T) at amino acid position 446 to be replaced by an alanine (A). 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
0.079
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Benign
0.88
DEOGEN2
Benign
0.20
T;T;T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.19
.;T;.
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.077
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.3
D;.;.
REVEL
Benign
0.061
Sift
Benign
0.035
D;.;.
Sift4G
Uncertain
0.026
D;D;D
Polyphen
0.0
B;B;B
Vest4
0.11
MutPred
0.33
Loss of phosphorylation at T446 (P = 0.0637);Loss of phosphorylation at T446 (P = 0.0637);Loss of phosphorylation at T446 (P = 0.0637);
MVP
0.15
MPC
0.13
ClinPred
0.057
T
GERP RS
0.94
Varity_R
0.097
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.

Other links and lift over

dbSNP: rs749069778; hg19: chr19-56895450; API