19-37564807-G-A

Variant summary

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

The NM_016536.5(ZNF571):​c.1621C>T​(p.Arg541Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,613,702 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 (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ZNF571
NM_016536.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.20
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=0.032380253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF571NM_016536.5 linkuse as main transcriptc.1621C>T p.Arg541Cys missense_variant 4/4 ENST00000451802.7
ZNF571-AS1NR_038248.1 linkuse as main transcriptn.338-1224G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF571ENST00000451802.7 linkuse as main transcriptc.1621C>T p.Arg541Cys missense_variant 4/41 NM_016536.5 P1
ZNF571-AS1ENST00000585578.5 linkuse as main transcriptn.210-1224G>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000856
AC:
13
AN:
151944
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000883
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000139
AC:
35
AN:
250988
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135654
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461642
Hom.:
0
Cov.:
34
AF XY:
0.0000674
AC XY:
49
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000531
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000855
AC:
13
AN:
152060
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000883
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000215
ExAC
AF:
0.0000988
AC:
12
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

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 GeneticsMar 20, 2024The c.1621C>T (p.R541C) 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 1621, causing the arginine (R) at amino acid position 541 to be replaced by a cysteine (C). 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
0.52
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Benign
0.85
DEOGEN2
Benign
0.024
T;T;T;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.000050
N
LIST_S2
Benign
0.21
T;.;.;.
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.032
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;M;M;M
MutationTaster
Benign
1.0
N;N;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-2.3
N;.;N;N
REVEL
Benign
0.061
Sift
Benign
0.13
T;.;T;T
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.43
B;B;B;B
Vest4
0.092
MVP
0.29
MPC
0.25
ClinPred
0.063
T
GERP RS
-0.83
Varity_R
0.058
gMVP
0.057

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: rs201347398; hg19: chr19-38055709; API