chr19-52405974-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032423.3(ZNF528):​c.83C>T​(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,612,022 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 6 hom. )

Consequence

ZNF528
NM_032423.3 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.706
Variant links:
Genes affected
ZNF528 (HGNC:29384): (zinc finger protein 528) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.015334696).
BP6
Variant 19-52405974-C-T is Benign according to our data. Variant chr19-52405974-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 782628.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF528NM_032423.3 linkc.83C>T p.Ala28Val missense_variant Exon 5 of 7 ENST00000360465.8 NP_115799.2 Q3MIS6-1
ZNF528XM_006723418.3 linkc.83C>T p.Ala28Val missense_variant Exon 4 of 8 XP_006723481.1
ZNF528XM_047439511.1 linkc.53C>T p.Ala18Val missense_variant Exon 2 of 6 XP_047295467.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF528ENST00000360465.8 linkc.83C>T p.Ala28Val missense_variant Exon 5 of 7 1 NM_032423.3 ENSP00000353652.3 Q3MIS6-1

Frequencies

GnomAD3 genomes
AF:
0.00200
AC:
305
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00291
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00200
AC:
503
AN:
251422
Hom.:
1
AF XY:
0.00219
AC XY:
297
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.000738
Gnomad AMR exome
AF:
0.00208
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00261
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.00280
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00277
AC:
4042
AN:
1459750
Hom.:
6
Cov.:
30
AF XY:
0.00279
AC XY:
2024
AN XY:
726146
show subpopulations
Gnomad4 AFR exome
AF:
0.000449
Gnomad4 AMR exome
AF:
0.00190
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00286
Gnomad4 FIN exome
AF:
0.000470
Gnomad4 NFE exome
AF:
0.00318
Gnomad4 OTH exome
AF:
0.00232
GnomAD4 genome
AF:
0.00200
AC:
305
AN:
152272
Hom.:
0
Cov.:
32
AF XY:
0.00180
AC XY:
134
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.000722
Gnomad4 AMR
AF:
0.00392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00208
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.00291
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00212
Hom.:
1
Bravo
AF:
0.00210
TwinsUK
AF:
0.00216
AC:
8
ALSPAC
AF:
0.00311
AC:
12
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00337
AC:
29
ExAC
AF:
0.00208
AC:
253
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00267
EpiControl
AF:
0.00338

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 07, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
14
DANN
Uncertain
0.98
DEOGEN2
Benign
0.013
.;T;T;T;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.056
T;T;T;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.015
T;T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
.;.;L;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.4
N;N;D;.;.
REVEL
Benign
0.10
Sift
Benign
0.22
T;T;T;.;.
Sift4G
Uncertain
0.029
D;D;T;D;D
Polyphen
0.81
.;.;P;.;.
Vest4
0.21
MVP
0.33
MPC
0.058
ClinPred
0.016
T
GERP RS
2.1
Varity_R
0.058
gMVP
0.047

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: rs141013163; hg19: chr19-52909227; COSMIC: COSV64621362; COSMIC: COSV64621362; API