chr19-56539076-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020828.2(ZFP28):c.58G>A(p.Ala20Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,527,090 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: 𝑓 0.000079 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056064308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.58G>A	p.Ala20Thr	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	NM_001308440.2 link	c.58G>A	p.Ala20Thr	missense_variant	Exon 1 of 7		NP_001295369.1	Q8NHY6-2
ZFP28	XM_011526463.4 link	c.182-549G>A		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4 link	c.-528G>A		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP28	ENST00000301318.8 link	c.58G>A	p.Ala20Thr	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5 link	c.58G>A	p.Ala20Thr	missense_variant	Exon 1 of 7	1		ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000594386.1 link	n.8G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
ZFP28	ENST00000589836.1 link	n.-54G>A		upstream_gene_variant		5		ENSP00000465853.1	K7EL00

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000317

AC:

AN:

126180

AF XY:

0.0000288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000260

GnomAD4 exome

AF:

0.00000582

AC:

AN:

1375186

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

678344

show subpopulations

African (AFR)

AF:

0.0000979

AC:

AN:

30638

American (AMR)

AF:

0.0000566

AC:

AN:

35354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24928

East Asian (EAS)

AF:

0.00

AC:

AN:

35120

South Asian (SAS)

AF:

0.00

AC:

AN:

78434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4096

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1074094

Other (OTH)

AF:

0.0000350

AC:

AN:

57152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151904

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41396

American (AMR)

AF:

0.000458

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67912

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000907

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.58G>A (p.A20T) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a G to A substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 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

0.091

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.69

N;N

PhyloP100

1.7

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.63

N;.

REVEL

Benign

0.054

Sift

Uncertain

0.019

D;.

Sift4G

Benign

0.069

T;D

Polyphen

0.037

B;.

Vest4

0.063

MutPred

0.23

Gain of phosphorylation at A20 (P = 6e-04);Gain of phosphorylation at A20 (P = 6e-04);

MVP

0.12

MPC

0.18

ClinPred

0.048

GERP RS

-0.53

PromoterAI

0.0060

Neutral

(source)

Varity_R

0.036

gMVP

0.10

Mutation Taster

=100/0

polymorphism

(source)

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

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

chr19-56539076-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over