NM_020828.2:c.191C>A

Variant names:

• chr19-56539209-C-A
• rs774922640
• NM_020828.2:c.191C>A

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.191C>A​(p.Thr64Lys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T64A) has been classified 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: -0.0660
• 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=0.0593642).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020828.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP28	NM_020828.2	MANE Select	c.191C>A	p.Thr64Lys	missense	Exon 1 of 8	NP_065879.1	Q8NHY6-1
	ZFP28	NM_001308440.2		c.191C>A	p.Thr64Lys	missense	Exon 1 of 7	NP_001295369.1	Q8NHY6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP28	ENST00000301318.8	TSL:1 MANE Select	c.191C>A	p.Thr64Lys	missense	Exon 1 of 8	ENSP00000301318.3	Q8NHY6-1
	ZFP28	ENST00000591844.5	TSL:1	c.191C>A	p.Thr64Lys	missense	Exon 1 of 7	ENSP00000468603.1	Q8NHY6-2
	ZFP28	ENST00000955594.1		c.191C>A	p.Thr64Lys	missense	Exon 1 of 7	ENSP00000625653.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.4
DANN	Benign	0.91
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.066
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.028
Sift	Benign	0.46	T
Sift4G	Benign	0.15	T
Polyphen		0.20	B
Vest4		0.14
MutPred		0.26		Loss of phosphorylation at T64 (P = 0.0223)
MVP		0.095
MPC		0.23
ClinPred		0.090	T
GERP RS		-0.62
PromoterAI		-0.096	Neutral
Varity_R		0.037
gMVP		0.092
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774922640; hg19: chr19-57050578;