19-56539059-C-A

Variant summary

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

The NM_020828.2(ZFP28):​c.41C>A​(p.Pro14Gln) 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. P14T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZFP28
NM_020828.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192
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 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=0.08762857).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZFP28NM_020828.2 linkc.41C>A p.Pro14Gln missense_variant Exon 1 of 8 ENST00000301318.8 NP_065879.1 Q8NHY6-1
ZFP28NM_001308440.2 linkc.41C>A p.Pro14Gln missense_variant Exon 1 of 7 NP_001295369.1 Q8NHY6-2
ZFP28XM_011526463.4 linkc.182-566C>A intron_variant Intron 1 of 7 XP_011524765.2
ZFP28XM_011526462.4 linkc.-545C>A upstream_gene_variant XP_011524764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZFP28ENST00000301318.8 linkc.41C>A p.Pro14Gln missense_variant Exon 1 of 8 1 NM_020828.2 ENSP00000301318.3 Q8NHY6-1
ZFP28ENST00000591844.5 linkc.41C>A p.Pro14Gln missense_variant Exon 1 of 7 1 ENSP00000468603.1 Q8NHY6-2
ZFP28ENST00000589836.1 linkn.-71C>A upstream_gene_variant 5 ENSP00000465853.1 K7EL00
ZFP28ENST00000594386.1 linkn.-10C>A upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1352192
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
666024
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 19, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.41C>A (p.P14Q) 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 41, causing the proline (P) at amino acid position 14 to be replaced by a glutamine (Q). 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
0.091
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
7.8
DANN
Benign
0.94
DEOGEN2
Benign
0.046
T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.55
N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.50
N;.
REVEL
Benign
0.012
Sift
Benign
0.079
T;.
Sift4G
Benign
0.17
T;D
Polyphen
0.047
B;.
Vest4
0.17
MutPred
0.21
Gain of MoRF binding (P = 0.0458);Gain of MoRF binding (P = 0.0458);
MVP
0.18
MPC
0.18
ClinPred
0.10
T
GERP RS
1.1
Varity_R
0.043
gMVP
0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57050428; API