chr19-42224969-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_133444.3(ZNF526):​c.566C>T​(p.Pro189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,236 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., cov: 32)
Exomes 𝑓: 0.012 ( 134 hom. )

Consequence

ZNF526
NM_133444.3 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.94
Variant links:
Genes affected
ZNF526 (HGNC:29415): (zinc finger protein 526) 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 -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0039301217).
BP6
Variant 19-42224969-C-T is Benign according to our data. Variant chr19-42224969-C-T is described in ClinVar as [Benign]. Clinvar id is 130838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF526NM_133444.3 linkuse as main transcriptc.566C>T p.Pro189Leu missense_variant 3/3 ENST00000301215.8
ZNF526NM_001314033.3 linkuse as main transcriptc.566C>T p.Pro189Leu missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF526ENST00000301215.8 linkuse as main transcriptc.566C>T p.Pro189Leu missense_variant 3/31 NM_133444.3 P1
ZNF526ENST00000710326.1 linkuse as main transcriptc.566C>T p.Pro189Leu missense_variant 3/3 P1

Frequencies

GnomAD3 genomes
AF:
0.00738
AC:
1123
AN:
152224
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00210
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00393
Gnomad FIN
AF:
0.00725
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0130
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00780
AC:
1961
AN:
251404
Hom.:
11
AF XY:
0.00785
AC XY:
1066
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00160
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.00119
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00310
Gnomad FIN exome
AF:
0.00698
Gnomad NFE exome
AF:
0.0136
Gnomad OTH exome
AF:
0.00749
GnomAD4 exome
AF:
0.0121
AC:
17714
AN:
1461894
Hom.:
134
Cov.:
32
AF XY:
0.0118
AC XY:
8564
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00170
Gnomad4 AMR exome
AF:
0.00279
Gnomad4 ASJ exome
AF:
0.00130
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00312
Gnomad4 FIN exome
AF:
0.00822
Gnomad4 NFE exome
AF:
0.0146
Gnomad4 OTH exome
AF:
0.00988
GnomAD4 genome
AF:
0.00737
AC:
1123
AN:
152342
Hom.:
5
Cov.:
32
AF XY:
0.00677
AC XY:
504
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00209
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00393
Gnomad4 FIN
AF:
0.00725
Gnomad4 NFE
AF:
0.0130
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.0121
Hom.:
16
Bravo
AF:
0.00701
TwinsUK
AF:
0.0111
AC:
41
ALSPAC
AF:
0.0140
AC:
54
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.0144
AC:
124
ExAC
AF:
0.00787
AC:
955
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0130
EpiControl
AF:
0.0127

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 18, 2014- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
14
DANN
Benign
0.53
DEOGEN2
Benign
0.0087
T
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.62
T
MetaRNN
Benign
0.0039
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
0.61
D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.060
Sift
Benign
0.67
T
Sift4G
Benign
0.13
T
Polyphen
0.0050
B
Vest4
0.29
MVP
0.46
MPC
0.35
ClinPred
0.0047
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.038
gMVP
0.34

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: rs150807158; hg19: chr19-42729121; COSMIC: COSV56630302; COSMIC: COSV56630302; API