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GeneBe

19-36449824-C-G

Variant summary

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

The NM_001145344.1(ZNF566):c.410G>C(p.Gly137Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,808 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF566
NM_001145344.1 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.407
Variant links:
Genes affected
ZNF566 (HGNC:25919): (zinc finger protein 566) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.061966836).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF566NM_001145344.1 linkuse as main transcriptc.410G>C p.Gly137Ala missense_variant 5/5 ENST00000452939.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF566ENST00000452939.7 linkuse as main transcriptc.410G>C p.Gly137Ala missense_variant 5/52 NM_001145344.1 P4Q969W8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251390
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000205
AC:
3
AN:
1461808
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 GeneticsMay 18, 2022The c.413G>C (p.G138A) alteration is located in exon 5 (coding exon 4) of the ZNF566 gene. This alteration results from a G to C substitution at nucleotide position 413, causing the glycine (G) at amino acid position 138 to be replaced by an alanine (A). 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
0.096
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.62
Cadd
Benign
12
Dann
Benign
0.63
DEOGEN2
Benign
0.025
T;T;.;T;.;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.061
T;T;T;.;T;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.062
T;T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.7
L;.;.;L;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.6
N;.;N;N;N;N
REVEL
Benign
0.021
Sift
Benign
0.66
T;.;T;T;T;T
Sift4G
Benign
0.75
T;T;T;T;.;.
Polyphen
0.14
B;.;.;B;.;.
Vest4
0.11
MutPred
0.30
Loss of disorder (P = 0.0702);.;.;Loss of disorder (P = 0.0702);Loss of disorder (P = 0.0702);.;
MVP
0.31
ClinPred
0.076
T
GERP RS
1.6
Varity_R
0.080
gMVP
0.049

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: rs374833866; hg19: chr19-36940726; API