chr19-37564753-C-G

Variant summary

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

The NM_016536.5(ZNF571):ā€‹c.1675G>Cā€‹(p.Glu559Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ZNF571
NM_016536.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.67
Variant links:
Genes affected
ZNF571 (HGNC:25000): (zinc finger protein 571) 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. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZNF571-AS1 (HGNC:44324): (ZNF571 antisense RNA 1)
ZNF540 (HGNC:25331): (zinc finger protein 540) Enables translation repressor activity, mRNA regulatory element binding. Involved in negative regulation of transcription, DNA-templated and negative regulation of translation. Located in cytosol and nucleoplasm. [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=0.024446696).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF571NM_016536.5 linkuse as main transcriptc.1675G>C p.Glu559Gln missense_variant 4/4 ENST00000451802.7
ZNF571-AS1NR_038248.1 linkuse as main transcriptn.338-1278C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF571ENST00000451802.7 linkuse as main transcriptc.1675G>C p.Glu559Gln missense_variant 4/41 NM_016536.5 P1
ZNF571-AS1ENST00000585578.5 linkuse as main transcriptn.210-1278C>G intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461512
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727050
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsNov 15, 2021The c.1675G>C (p.E559Q) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a G to C substitution at nucleotide position 1675, causing the glutamic acid (E) at amino acid position 559 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
0.10
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0038
T;T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.000020
N
LIST_S2
Benign
0.034
T;.;.;.
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.024
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.39
N;N;N;N
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.3
N;.;N;N
REVEL
Benign
0.033
Sift
Benign
0.29
T;.;T;T
Sift4G
Benign
0.067
T;T;T;T
Polyphen
0.0060
B;B;B;B
Vest4
0.071
MutPred
0.29
Loss of ubiquitination at K561 (P = 0.0347);Loss of ubiquitination at K561 (P = 0.0347);Loss of ubiquitination at K561 (P = 0.0347);Loss of ubiquitination at K561 (P = 0.0347);
MVP
0.099
MPC
0.038
ClinPred
0.074
T
GERP RS
-1.8
Varity_R
0.11
gMVP
0.018

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-38055655; API