NM_020828.2:c.577G>A

Variant names:

• chr19-56549011-G-A
• rs142184982
• NM_020828.2:c.577G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020828.2(ZFP28):​c.577G>A​(p.Glu193Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,613,932 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00028 (0 hom.)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.324
• Publications: 5 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055898964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.577G>A	p.Glu193Lys	missense_variant	Exon 5 of 8	ENST00000301318.8	NP_065879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.577G>A	p.Glu193Lys	missense_variant	Exon 5 of 8	1	NM_020828.2	ENSP00000301318.3

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152142 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 33 AN: 251356 AF XY: 0.000125

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000275 AC: 402 AN: 1461790 Hom.: 0 Cov.: 32 AF XY: 0.000275 AC XY: 200 AN XY: 727200

African (AFR) AF: 0.000149 AC: 5 AN: 33476

American (AMR) AF: 0.000179 AC: 8 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39686

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000324 AC: 360 AN: 1111972

Other (OTH) AF: 0.000331 AC: 20 AN: 60392

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152142 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74314

African (AFR) AF: 0.000169 AC: 7 AN: 41440

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000854 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.577G>A (p.E193K) alteration is located in exon 5 (coding exon 5) of the ZFP28 gene. This alteration results from a G to A substitution at nucleotide position 577, causing the glutamic acid (E) at amino acid position 193 to be replaced by a lysine (K). 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	0.081
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.24	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.056	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L;L
PhyloP100		0.32
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.11
Sift	Benign	0.36	T;.
Sift4G	Benign	0.29	T;T
Polyphen		0.0080	B;.
Vest4		0.18
MVP		0.17
MPC		0.21
ClinPred		0.031	T
GERP RS		0.87
Varity_R		0.083
gMVP		0.25
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142184982; hg19: chr19-57060380; COSMIC: COSV56735248; COSMIC: COSV56735248;