Genetic Variant NM_020828.2:c.682C>A (chr19-56549116-C-A) – 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.682C>A(p.Gln228Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783

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:

ZNF470-DT (HGNC:55272): (ZNF470 divergent transcript)

ZNF470-DT 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=0.12626225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.682C>A	p.Gln228Lys	missense_variant	Exon 5 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8 link	c.682C>A	p.Gln228Lys	missense_variant	Exon 5 of 8	1	NM_020828.2	ENSP00000301318.3		Q8NHY6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

240396

AF XY:

0.00000771

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000630

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1450434

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720516

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33080

American (AMR)

AF:

0.0000466

AC:

AN:

42922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25680

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.00

AC:

AN:

83596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106804

Other (OTH)

AF:

0.00

AC:

AN:

59966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000600

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.682C>A (p.Q228K) alteration is located in exon 5 (coding exon 5) of the ZFP28 gene. This alteration results from a C to A substitution at nucleotide position 682, causing the glutamine (Q) at amino acid position 228 to be replaced by a lysine (K). 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

0.082

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;L

PhyloP100

0.78

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.036

Sift

Benign

0.066

T;.

Sift4G

Benign

0.33

T;T

Polyphen

0.075

B;.

Vest4

0.28

MutPred

0.39

Gain of ubiquitination at Q228 (P = 0.0121);Gain of ubiquitination at Q228 (P = 0.0121);

MVP

0.27

MPC

0.24

ClinPred

0.074

GERP RS

3.2

Varity_R

0.16

gMVP

0.23

Mutation Taster

=99/1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over