19-56539058-C-A

Variant summary

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

The NM_020828.2(ZFP28):​c.40C>A​(p.Pro14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

ZFP28
NM_020828.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.414
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]

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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=0.06353572).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFP28NM_020828.2 linkc.40C>A p.Pro14Thr missense_variant Exon 1 of 8 ENST00000301318.8 NP_065879.1 Q8NHY6-1
ZFP28NM_001308440.2 linkc.40C>A p.Pro14Thr missense_variant Exon 1 of 7 NP_001295369.1 Q8NHY6-2
ZFP28XM_011526463.4 linkc.182-567C>A intron_variant Intron 1 of 7 XP_011524765.2
ZFP28XM_011526462.4 linkc.-546C>A upstream_gene_variant XP_011524764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFP28ENST00000301318.8 linkc.40C>A p.Pro14Thr missense_variant Exon 1 of 8 1 NM_020828.2 ENSP00000301318.3 Q8NHY6-1
ZFP28ENST00000591844.5 linkc.40C>A p.Pro14Thr missense_variant Exon 1 of 7 1 ENSP00000468603.1 Q8NHY6-2
ZFP28ENST00000589836.1 linkn.-72C>A upstream_gene_variant 5 ENSP00000465853.1 K7EL00
ZFP28ENST00000594386.1 linkn.-11C>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.40C>A (p.P14T) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a C to A substitution at nucleotide position 40, causing the proline (P) at amino acid position 14 to be replaced by a threonine (T). 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
0.071
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.85
DANN
Benign
0.90
DEOGEN2
Benign
0.028
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.064
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.61
N;.
REVEL
Benign
0.0050
Sift
Benign
0.23
T;.
Sift4G
Benign
0.34
T;D
Polyphen
0.0020
B;.
Vest4
0.076
MutPred
0.21
Gain of phosphorylation at P14 (P = 0.0115);Gain of phosphorylation at P14 (P = 0.0115);
MVP
0.088
MPC
0.20
ClinPred
0.040
T
GERP RS
-4.4
Varity_R
0.033
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs2044166737; hg19: chr19-57050427; API