chr19-56384238-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_001320371.4(ZNF582):ā€‹c.1179A>Gā€‹(p.Lys393=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,613,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: š‘“ 0.00076 ( 1 hom., cov: 32)
Exomes š‘“: 0.000069 ( 0 hom. )

Consequence

ZNF582
NM_001320371.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.652
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 19-56384238-T-C is Benign according to our data. Variant chr19-56384238-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033172.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-0.652 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF582NM_001320371.4 linkuse as main transcriptc.1179A>G p.Lys393= synonymous_variant 5/5 ENST00000586929.6 NP_001307300.2
ZNF582NM_144690.3 linkuse as main transcriptc.1179A>G p.Lys393= synonymous_variant 5/5 NP_653291.1
ZNF582XR_007066621.1 linkuse as main transcriptn.1352A>G non_coding_transcript_exon_variant 5/6
ZNF582XR_430188.4 linkuse as main transcriptn.1574A>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.1179A>G p.Lys393= synonymous_variant 5/51 NM_001320371.4 ENSP00000465619 P1
ZNF582ENST00000301310.8 linkuse as main transcriptc.1179A>G p.Lys393= synonymous_variant 5/51 ENSP00000301310 P1
ZNF582ENST00000589143.5 linkuse as main transcriptc.232+5763A>G intron_variant 5 ENSP00000468679
ZNF582ENST00000589895.2 linkuse as main transcriptc.232+5763A>G intron_variant 2 ENSP00000465639

Frequencies

GnomAD3 genomes
AF:
0.000756
AC:
115
AN:
152020
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00268
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00143
GnomAD3 exomes
AF:
0.000251
AC:
63
AN:
251182
Hom.:
1
AF XY:
0.000192
AC XY:
26
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.00351
Gnomad AMR exome
AF:
0.000174
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
AF:
0.0000691
AC:
101
AN:
1461766
Hom.:
0
Cov.:
33
AF XY:
0.0000564
AC XY:
41
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.00248
Gnomad4 AMR exome
AF:
0.000134
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:
0.00000809
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000756
AC:
115
AN:
152138
Hom.:
1
Cov.:
32
AF XY:
0.000672
AC XY:
50
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.00268
Gnomad4 AMR
AF:
0.0000654
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:
0.00142
Alfa
AF:
0.000502
Hom.:
0
Bravo
AF:
0.000812
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ZNF582-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJun 12, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.7
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs139795329; hg19: chr19-56895607; COSMIC: COSV56732441; COSMIC: COSV56732441; API