Genetic Variant ZFP28:p.Leu53Phe (chr19-56539175-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_020828.2(ZFP28):c.157C>T(p.Leu53Phe) 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. 14/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.389

Publications

1 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=0.06240374).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP28	NM_020828.2	MANE Select	c.157C>T	p.Leu53Phe	missense	Exon 1 of 8	NP_065879.1	Q8NHY6-1
	ZFP28	NM_001308440.2		c.157C>T	p.Leu53Phe	missense	Exon 1 of 7	NP_001295369.1	Q8NHY6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP28	ENST00000301318.8	TSL:1 MANE Select	c.157C>T	p.Leu53Phe	missense	Exon 1 of 8	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5	TSL:1	c.157C>T	p.Leu53Phe	missense	Exon 1 of 7	ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000955594.1		c.157C>T	p.Leu53Phe	missense	Exon 1 of 7	ENSP00000625653.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1450850

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721510

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39414

South Asian (SAS)

AF:

0.00

AC:

AN:

85034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109956

Other (OTH)

AF:

0.00

AC:

AN:

60056

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.67

M_CAP

Benign

0.0079

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

PhyloP100

-0.39

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.33

REVEL

Benign

0.014

Sift

Benign

0.12

Sift4G

Benign

0.22

Polyphen

0.12

Vest4

0.061

MutPred

0.13

Gain of phosphorylation at S55 (P = 0.2086)

MVP

0.11

MPC

0.22

ClinPred

0.090

GERP RS

0.74

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.083

gMVP

0.076

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over