chr19-37425875-G-C

Variant summary

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

The NM_152484.3(ZNF569):ā€‹c.231C>Gā€‹(p.His77Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,374 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: not found (cov: 31)
Exomes š‘“: 0.0000068 ( 0 hom. )

Consequence

ZNF569
NM_152484.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26
Variant links:
Genes affected
ZNF569 (HGNC:24737): (zinc finger protein 569) 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 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=0.048314244).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF569NM_152484.3 linkc.231C>G p.His77Gln missense_variant 5/6 ENST00000316950.11 NP_689697.2 Q5MCW4-1A0A024R0G4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF569ENST00000316950.11 linkc.231C>G p.His77Gln missense_variant 5/61 NM_152484.3 ENSP00000325018.5 Q5MCW4-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251416
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135882
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:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000684
AC:
10
AN:
1461374
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727028
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:
0.00000900
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000936
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
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 07, 2022The c.231C>G (p.H77Q) alteration is located in exon 5 (coding exon 3) of the ZNF569 gene. This alteration results from a C to G substitution at nucleotide position 231, causing the histidine (H) at amino acid position 77 to be replaced by a glutamine (Q). 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
0.083
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
14
DANN
Benign
0.86
DEOGEN2
Benign
0.034
T;T;.;.
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.018
.;T;.;T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.048
T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
0.0
N;N;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
1.0
N;N;.;.
REVEL
Benign
0.016
Sift
Benign
1.0
T;T;.;.
Sift4G
Benign
0.64
T;T;.;T
Polyphen
0.42
B;B;.;.
Vest4
0.19
MutPred
0.41
Gain of disorder (P = 0.0895);Gain of disorder (P = 0.0895);.;.;
MVP
0.23
MPC
0.13
ClinPred
0.031
T
GERP RS
2.2
Varity_R
0.060
gMVP
0.024

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs369850686; hg19: chr19-37916777; API