Genetic Variant ZFP28:p.Pro25Arg (chr19-56539092-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020828.2(ZFP28):c.74C>G(p.Pro25Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,388,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.258

Publications

0 publications found

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]

ZFP28 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12478876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.74C>G	p.Pro25Arg	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	NM_001308440.2 link	c.74C>G	p.Pro25Arg	missense_variant	Exon 1 of 7		NP_001295369.1	Q8NHY6-2
ZFP28	XM_011526463.4 link	c.182-533C>G		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4 link	c.-512C>G		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP28	ENST00000301318.8 link	c.74C>G	p.Pro25Arg	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5 link	c.74C>G	p.Pro25Arg	missense_variant	Exon 1 of 7	1		ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000594386.1 link	n.24C>G		non_coding_transcript_exon_variant	Exon 1 of 3	2
ZFP28	ENST00000589836.1 link	n.-38C>G		upstream_gene_variant		5		ENSP00000465853.1	K7EL00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.20e-7

AC:

AN:

1388688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31504

American (AMR)

AF:

0.00

AC:

AN:

36462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.00

AC:

AN:

35866

South Asian (SAS)

AF:

0.00

AC:

AN:

79382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4314

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1081154

Other (OTH)

AF:

0.00

AC:

AN:

57840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Apr 22, 2024

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;N

PhyloP100

-0.26

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.75

N;.

REVEL

Benign

0.063

Sift

Benign

0.34

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.87

P;.

Vest4

0.25

MutPred

0.22

Gain of methylation at P25 (P = 0.0056);Gain of methylation at P25 (P = 0.0056);

MVP

0.41

MPC

0.21

ClinPred

0.33

GERP RS

2.5

PromoterAI

0.026

Neutral

(source)

Varity_R

0.074

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr19-56539092-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over