chr19-56384222-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320371.4(ZNF582):ā€‹c.1195G>Cā€‹(p.Val399Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,398 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‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.000012 ( 0 hom. )

Consequence

ZNF582
NM_001320371.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.580
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058374852).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF582NM_001320371.4 linkuse as main transcriptc.1195G>C p.Val399Leu missense_variant 5/5 ENST00000586929.6 NP_001307300.2
ZNF582NM_144690.3 linkuse as main transcriptc.1195G>C p.Val399Leu missense_variant 5/5 NP_653291.1
ZNF582XR_007066621.1 linkuse as main transcriptn.1368G>C non_coding_transcript_exon_variant 5/6
ZNF582XR_430188.4 linkuse as main transcriptn.1590G>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.1195G>C p.Val399Leu missense_variant 5/51 NM_001320371.4 ENSP00000465619 P1
ZNF582ENST00000301310.8 linkuse as main transcriptc.1195G>C p.Val399Leu missense_variant 5/51 ENSP00000301310 P1
ZNF582ENST00000589143.5 linkuse as main transcriptc.232+5779G>C intron_variant 5 ENSP00000468679
ZNF582ENST00000589895.2 linkuse as main transcriptc.232+5779G>C intron_variant 2 ENSP00000465639

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151942
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250822
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135544
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:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461456
Hom.:
0
Cov.:
33
AF XY:
0.0000124
AC XY:
9
AN XY:
726996
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:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151942
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74206
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 GeneticsJun 16, 2024The c.1195G>C (p.V399L) alteration is located in exon 5 (coding exon 4) of the ZNF582 gene. This alteration results from a G to C substitution at nucleotide position 1195, causing the valine (V) at amino acid position 399 to be replaced by a leucine (L). 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
0.26
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
19
DANN
Benign
0.96
DEOGEN2
Benign
0.031
T;T;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.28
.;T;.
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.058
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-0.030
N;N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.1
N;.;.
REVEL
Benign
0.071
Sift
Uncertain
0.010
D;.;.
Sift4G
Benign
0.065
T;T;T
Polyphen
0.016
B;B;B
Vest4
0.064
MutPred
0.54
Loss of MoRF binding (P = 0.0965);Loss of MoRF binding (P = 0.0965);Loss of MoRF binding (P = 0.0965);
MVP
0.076
MPC
0.18
ClinPred
0.16
T
GERP RS
2.1
Varity_R
0.11
gMVP
0.063

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: rs1184260914; hg19: chr19-56895591; API