dbSNP rs757228568: ZFP28:p.Arg48His (chr19-56539161-G-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.143G>A(p.Arg48His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R48P) 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

Not reported in ClinVar

Conservation

PhyloP100: 0.231

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:

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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=0.14922118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.143G>A	p.Arg48His	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	NM_001308440.2 link	c.143G>A	p.Arg48His	missense_variant	Exon 1 of 7		NP_001295369.1	Q8NHY6-2
ZFP28	XM_011526463.4 link	c.182-464G>A		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4 link	c.-443G>A		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP28	ENST00000301318.8 link	c.143G>A	p.Arg48His	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3	Q8NHY6-1
ZFP28	ENST00000591844.5 link	c.143G>A	p.Arg48His	missense_variant	Exon 1 of 7	1		ENSP00000468603.1	Q8NHY6-2
ZFP28	ENST00000589836.1 link	n.32G>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000465853.1	K7EL00
ZFP28	ENST00000594386.1 link	n.93G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1448486

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720174

African (AFR)

AF:

0.00

AC:

AN:

33306

American (AMR)

AF:

0.00

AC:

AN:

44020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25920

East Asian (EAS)

AF:

0.00

AC:

AN:

39268

South Asian (SAS)

AF:

0.00

AC:

AN:

84730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46720

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109018

Other (OTH)

AF:

0.00

AC:

AN:

59988

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.083

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L

PhyloP100

0.23

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.63

N;.

REVEL

Benign

0.045

Sift

Uncertain

0.018

D;.

Sift4G

Uncertain

0.044

D;D

Polyphen

0.94

P;.

Vest4

0.18

MutPred

0.34

Loss of methylation at R48 (P = 0.0071);Loss of methylation at R48 (P = 0.0071);

MVP

0.33

MPC

0.22

ClinPred

0.56

GERP RS

2.9

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.099

gMVP

0.13

Mutation Taster

=80/20

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over