19-56547812-T-C

Variant names:

• chr19-56547812-T-C
• NM_020828.2:c.433T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020828.2(ZFP28):​c.433T>C​(p.Cys145Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.612
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31562763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.433T>C	p.Cys145Arg	missense_variant	Exon 4 of 8	ENST00000301318.8	NP_065879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.433T>C	p.Cys145Arg	missense_variant	Exon 4 of 8	1	NM_020828.2	ENSP00000301318.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.433T>C (p.C145R) alteration is located in exon 4 (coding exon 4) of the ZFP28 gene. This alteration results from a T to C substitution at nucleotide position 433, causing the cysteine (C) at amino acid position 145 to be replaced by an arginine (R). 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	Uncertain	0.52
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	0.096
Eigen_PC	Benign	-0.0031
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.088	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		0.61
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Benign	0.20
Sift	Benign	0.068	T;.
Sift4G	Benign	0.48	T;D
Polyphen		1.0	D;.
Vest4		0.75
MutPred		0.40		Gain of MoRF binding (P = 0.0029);Gain of MoRF binding (P = 0.0029);
MVP		0.37
MPC		0.91
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.70
gMVP		0.30
Mutation Taster		=74/26	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

hg19: chr19-57059181;