19-56539209-C-T

Variant names:

• chr19-56539209-C-T
• rs774922640
• NM_020828.2:c.191C>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.191C>T​(p.Thr64Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,444,766 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. 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. T64A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.052045375).

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>T	p.Thr64Met	missense	Exon 1 of 8	NP_065879.1	Q8NHY6-1
	ZFP28	NM_001308440.2		c.191C>T	p.Thr64Met	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>T	p.Thr64Met	missense	Exon 1 of 8	ENSP00000301318.3	Q8NHY6-1
	ZFP28	ENST00000591844.5	TSL:1	c.191C>T	p.Thr64Met	missense	Exon 1 of 7	ENSP00000468603.1	Q8NHY6-2
	ZFP28	ENST00000955594.1		c.191C>T	p.Thr64Met	missense	Exon 1 of 7	ENSP00000625653.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000142 AC: 3 AN: 210962 AF XY: 0.0000171

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: 0.0000746

Gnomad NFE exome AF: 0.0000107

Gnomad OTH exome AF: 0.000185

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1444766 Hom.: 0 Cov.: 34 AF XY: 0.00000418 AC XY: 3 AN XY: 718124

African (AFR) AF: 0.00 AC: 0 AN: 33288

American (AMR) AF: 0.00 AC: 0 AN: 43640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107966

Other (OTH) AF: 0.0000167 AC: 1 AN: 59924

GnomAD4 genome Cov.: 31

Alfa AF: 0.000144 Hom.: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.066
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.59	N
REVEL	Benign	0.045
Sift	Benign	0.15	T
Sift4G	Uncertain	0.048	D
Polyphen		0.017	B
Vest4		0.11
MutPred		0.22		Loss of phosphorylation at T64 (P = 0.0223)
MVP		0.088
MPC		0.19
ClinPred		0.026	T
GERP RS		-0.62
PromoterAI		-0.090	Neutral
Varity_R		0.018
gMVP		0.082
Mutation Taster		=97/3	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: rs774922640; hg19: chr19-57050578; COSMIC: COSV56737726; COSMIC: COSV56737726;