chr19-56539124-C-T

Variant names:

• chr19-56539124-C-T
• NM_020828.2:c.106C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020828.2(ZFP28):​c.106C>T​(p.Pro36Ser) 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 (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.305
• 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]

ACMG classification

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=0.054999292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1
ZFP28	NM_001308440.2	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 7		NP_001295369.1
ZFP28	XM_011526463.4	c.182-501C>T		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4	c.-480C>T		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3
ZFP28	ENST00000591844.5	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 7	1		ENSP00000468603.1
ZFP28	ENST00000594386.1	n.56C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
ZFP28	ENST00000589836.1	n.-6C>T		upstream_gene_variant		5		ENSP00000465853.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.P36S) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 to be replaced by a serine (S). 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	0.083
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.34	N;N
PhyloP100		-0.30
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.83	N;.
REVEL	Benign	0.021
Sift	Benign	0.67	T;.
Sift4G	Benign	0.80	T;T
Polyphen		0.0020	B;.
Vest4		0.085
MutPred		0.17		Gain of glycosylation at P36 (P = 0.0199);Gain of glycosylation at P36 (P = 0.0199);
MVP		0.20
MPC		0.18
ClinPred		0.062	T
GERP RS		-2.9
PromoterAI		0.045	Neutral
Varity_R		0.025
gMVP		0.17
Mutation Taster		=98/2	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: chr19-57050493;