chr19-56539080-C-T

Variant summary

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

The NM_020828.2(ZFP28):​c.62C>T​(p.Pro21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,532,530 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 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.559
Variant links:
Genes affected
ZFP28 (HGNC:17801): (ZFP28 zinc finger protein) 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. Predicted to be active in nucleus. [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=0.03748676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFP28NM_020828.2 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 8 ENST00000301318.8 NP_065879.1 Q8NHY6-1
ZFP28NM_001308440.2 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 7 NP_001295369.1 Q8NHY6-2
ZFP28XM_011526463.4 linkc.182-545C>T intron_variant Intron 1 of 7 XP_011524765.2
ZFP28XM_011526462.4 linkc.-524C>T upstream_gene_variant XP_011524764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFP28ENST00000301318.8 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 8 1 NM_020828.2 ENSP00000301318.3 Q8NHY6-1
ZFP28ENST00000591844.5 linkc.62C>T p.Pro21Leu missense_variant Exon 1 of 7 1 ENSP00000468603.1 Q8NHY6-2
ZFP28ENST00000594386.1 linkn.12C>T non_coding_transcript_exon_variant Exon 1 of 3 2
ZFP28ENST00000589836.1 linkn.-50C>T upstream_gene_variant 5 ENSP00000465853.1 K7EL00

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
151916
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.000221
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000614
AC:
8
AN:
130384
Hom.:
0
AF XY:
0.0000278
AC XY:
2
AN XY:
71858
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:
0.000164
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000165
AC:
228
AN:
1380614
Hom.:
0
Cov.:
34
AF XY:
0.000166
AC XY:
113
AN XY:
681408
show subpopulations
Gnomad4 AFR exome
AF:
0.0000322
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:
0.000204
Gnomad4 OTH exome
AF:
0.000122
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
151916
Hom.:
0
Cov.:
31
AF XY:
0.0000539
AC XY:
4
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.000221
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000452
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000482
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 22, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>T (p.P21L) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a C to T substitution at nucleotide position 62, causing the proline (P) at amino acid position 21 to be replaced by a leucine (L). 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
0.094
BayesDel_addAF
Benign
-0.69
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
4.3
DANN
Benign
0.97
DEOGEN2
Benign
0.016
T;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.14
N;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.91
N;.
REVEL
Benign
0.013
Sift
Benign
0.94
T;.
Sift4G
Benign
0.57
T;T
Polyphen
0.0
B;.
Vest4
0.090
MutPred
0.22
Loss of glycosylation at P21 (P = 0.0229);Loss of glycosylation at P21 (P = 0.0229);
MVP
0.081
MPC
0.18
ClinPred
0.043
T
GERP RS
-4.8
Varity_R
0.021
gMVP
0.081

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: rs553987932; hg19: chr19-57050449; API