Genetic Variant NM_020828.2:c.41C>A (chr19-56539059-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.41C>A(p.Pro14Gln) 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. 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. P14T) has been classified 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: 0.192

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=0.08762857).

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.41C>A	p.Pro14Gln	missense	Exon 1 of 8	NP_065879.1	Q8NHY6-1
	ZFP28	NM_001308440.2		c.41C>A	p.Pro14Gln	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.41C>A	p.Pro14Gln	missense	Exon 1 of 8	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5	TSL:1	c.41C>A	p.Pro14Gln	missense	Exon 1 of 7	ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000955594.1		c.41C>A	p.Pro14Gln	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:

1352192

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

666024

African (AFR)

AF:

0.00

AC:

AN:

28778

American (AMR)

AF:

0.00

AC:

AN:

31106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24006

East Asian (EAS)

AF:

0.00

AC:

AN:

33978

South Asian (SAS)

AF:

0.00

AC:

AN:

76994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33994

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3944

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1063450

Other (OTH)

AF:

0.00

AC:

AN:

55942

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

0.091

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.8

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.046

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.51

M_CAP

Benign

0.0065

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.55

PhyloP100

0.19

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.50

REVEL

Benign

0.012

Sift

Benign

0.079

Sift4G

Benign

0.17

Polyphen

0.047

Vest4

0.17

MutPred

0.21

Gain of MoRF binding (P = 0.0458)

MVP

0.18

MPC

0.18

ClinPred

0.10

GERP RS

1.1

PromoterAI

0.032

Neutral

(source)

Varity_R

0.043

gMVP

0.12

Mutation Taster

=96/4

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