19-37564675-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016536.5(ZNF571):​c.1753C>T​(p.Pro585Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ZNF571
NM_016536.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
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]
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29698738).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF571NM_016536.5 linkuse as main transcriptc.1753C>T p.Pro585Ser missense_variant 4/4 ENST00000451802.7 NP_057620.3 Q7Z3V5A0A024R0L0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF571ENST00000451802.7 linkuse as main transcriptc.1753C>T p.Pro585Ser missense_variant 4/41 NM_016536.5 ENSP00000392638.1 Q7Z3V5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250676
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135502
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461034
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
726806
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:
0.00000630
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 GeneticsAug 12, 2022The c.1753C>T (p.P585S) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a C to T substitution at nucleotide position 1753, causing the proline (P) at amino acid position 585 to be replaced by a serine (S). 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
Uncertain
0.55
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.028
T;T;T;T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.00035
N
LIST_S2
Benign
0.76
T;.;.;.
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.30
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L;L;L
PrimateAI
Benign
0.34
T
PROVEAN
Pathogenic
-5.7
D;.;D;D
REVEL
Benign
0.099
Sift
Uncertain
0.0010
D;.;D;D
Sift4G
Uncertain
0.019
D;D;D;D
Polyphen
0.98
D;D;D;D
Vest4
0.25
MVP
0.37
MPC
0.23
ClinPred
0.96
D
GERP RS
2.5
Varity_R
0.30
gMVP
0.036

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: rs1201271797; hg19: chr19-38055577; API