19-56539208-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020828.2(ZFP28):c.190A>G(p.Thr64Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000831 in 1,443,302 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T64K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.20

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04216832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.190A>G	p.Thr64Ala	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	NM_001308440.2 link	c.190A>G	p.Thr64Ala	missense_variant	Exon 1 of 7		NP_001295369.1	Q8NHY6-2
ZFP28	XM_011526463.4 link	c.182-417A>G		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4 link	c.-396A>G		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP28	ENST00000301318.8 link	c.190A>G	p.Thr64Ala	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5 link	c.190A>G	p.Thr64Ala	missense_variant	Exon 1 of 7	1		ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000589836.1 link	n.79A>G		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000465853.1	K7EL00
ZFP28	ENST00000594386.1 link	n.140A>G		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000831

AC:

AN:

1443302

Hom.:

Cov.:

AF XY:

0.00000697

AC XY:

AN XY:

717198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33262

American (AMR)

AF:

0.00

AC:

AN:

43430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39234

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5104

European-Non Finnish (NFE)

AF:

0.00000903

AC:

AN:

1107566

Other (OTH)

AF:

0.0000167

AC:

AN:

59858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.190A>G (p.T64A) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the threonine (T) at amino acid position 64 to be replaced by an alanine (A). 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

0.060

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.072

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0099

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

N;N

PhyloP100

-2.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.31

N;.

REVEL

Benign

0.0040

Sift

Benign

0.61

T;.

Sift4G

Benign

0.43

T;T

Polyphen

0.0

B;.

Vest4

0.053

MutPred

0.17

Loss of phosphorylation at T64 (P = 0.0223);Loss of phosphorylation at T64 (P = 0.0223);

MVP

0.076

MPC

0.17

ClinPred

0.045

GERP RS

-5.2

PromoterAI

0.062

Neutral

(source)

Varity_R

0.026

gMVP

0.061

Mutation Taster

=100/0

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

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19-56539208-A-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