dbSNP rs149264851: ZFP28:p.His305Arg (chr19-56553699-A-G) – 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.914A>G(p.His305Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,457,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. H305L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ZFP28
NM_020828.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.37

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:

ZNF470-DT (HGNC:55272): (ZNF470 divergent transcript)

ZNF470-DT 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=0.044815004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2 link	c.914A>G	p.His305Arg	missense_variant	Exon 8 of 8	ENST00000301318.8	NP_065879.1	Q8NHY6-1
ZFP28	XM_011526463.4 link	c.887A>G	p.His296Arg	missense_variant	Exon 8 of 8		XP_011524765.2
ZFP28	XM_011526462.4 link	c.623A>G	p.His208Arg	missense_variant	Exon 8 of 8		XP_011524764.1
ZNF470-DT	XM_047439806.1 link	c.*11-6428T>C		intron_variant	Intron 1 of 1		XP_047295762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8 link	c.914A>G	p.His305Arg	missense_variant	Exon 8 of 8	1	NM_020828.2	ENSP00000301318.3		Q8NHY6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000808

AC:

AN:

247504

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000446

AC:

AN:

1457550

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33300

American (AMR)

AF:

0.00

AC:

AN:

44090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25814

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

85428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000568

AC:

AN:

1110122

Other (OTH)

AF:

0.0000332

AC:

AN:

60164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.89

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.025

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0099

LIST_S2

Benign

0.0066

M_CAP

Benign

0.0032

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.11

PhyloP100

-1.4

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.14

REVEL

Benign

0.0080

Sift

Benign

0.35

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.037

MVP

0.10

MPC

0.22

ClinPred

0.072

GERP RS

-3.9

Varity_R

0.037

gMVP

0.043

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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rs149264851

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over