19-37564989-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016536.5(ZNF571):​c.1439G>T​(p.Gly480Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,744 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: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF571
NM_016536.5 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17473882).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF571NM_016536.5 linkuse as main transcriptc.1439G>T p.Gly480Val missense_variant 4/4 ENST00000451802.7
ZNF571-AS1NR_038248.1 linkuse as main transcriptn.338-1042C>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.1439G>T p.Gly480Val missense_variant 4/41 NM_016536.5 P1
ZNF571-AS1ENST00000585578.5 linkuse as main transcriptn.210-1042C>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000580
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000677
AC:
17
AN:
251112
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135732
show subpopulations
Gnomad AFR exome
AF:
0.000985
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461660
Hom.:
0
Cov.:
34
AF XY:
0.0000206
AC XY:
15
AN XY:
727140
show subpopulations
Gnomad4 AFR exome
AF:
0.000687
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000828
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.000580
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000159
Hom.:
0
Bravo
AF:
0.000189
ESP6500AA
AF:
0.00136
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10

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 GeneticsSep 14, 2022The c.1439G>T (p.G480V) alteration is located in exon 4 (coding exon 3) of the ZNF571 gene. This alteration results from a G to T substitution at nucleotide position 1439, causing the glycine (G) at amino acid position 480 to be replaced by a valine (V). 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
Pathogenic
0.64
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.0027
N
LIST_S2
Benign
0.15
T;.;.;.
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Pathogenic
3.2
M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-7.2
D;.;D;D
REVEL
Benign
0.20
Sift
Pathogenic
0.0
D;.;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.29
MVP
0.45
MPC
0.25
ClinPred
0.91
D
GERP RS
2.5
Varity_R
0.67
gMVP
0.060

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: rs145299773; hg19: chr19-38055891; API