19-56539023-G-A

Variant names:

• chr19-56539023-G-A
• rs541673443
• NM_020828.2:c.5G>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.5G>A​(p.Arg2Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,428,528 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 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. R2P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000017 (1 hom.)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008525461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.5G>A	p.Arg2Gln	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1
ZFP28	NM_001308440.2	c.5G>A	p.Arg2Gln	missense_variant	Exon 1 of 7		NP_001295369.1
ZFP28	XM_011526463.4	c.182-602G>A		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4	c.-581G>A		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.5G>A	p.Arg2Gln	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3
ZFP28	ENST00000591844.5	c.5G>A	p.Arg2Gln	missense_variant	Exon 1 of 7	1		ENSP00000468603.1
ZFP28	ENST00000589836.1	n.-107G>A		upstream_gene_variant		5		ENSP00000465853.1
ZFP28	ENST00000594386.1	n.-46G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151446 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000201 AC: 1 AN: 49762 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000172 AC: 22 AN: 1276974 Hom.: 1 Cov.: 32 AF XY: 0.0000257 AC XY: 16 AN XY: 623280

African (AFR) AF: 0.00 AC: 0 AN: 25672

American (AMR) AF: 0.00 AC: 0 AN: 20360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18762

East Asian (EAS) AF: 0.00 AC: 0 AN: 32022

South Asian (SAS) AF: 0.000331 AC: 21 AN: 63356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1030094

Other (OTH) AF: 0.0000190 AC: 1 AN: 52722

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151554 Hom.: 0 Cov.: 30 AF XY: 0.0000270 AC XY: 2 AN XY: 74086

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5072

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67764

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000135 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.0085	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.26	N;N
PhyloP100		-0.34
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.25	N;.
REVEL	Benign	0.016
Sift	Benign	0.66	T;.
Sift4G	Benign	0.61	T;T
Polyphen		0.0010	B;.
Vest4		0.058
MutPred		0.23		Loss of methylation at R2 (P = 0.0031);Loss of methylation at R2 (P = 0.0031);
MVP		0.14
MPC		0.21
ClinPred		0.026	T
GERP RS		-1.8
PromoterAI		-0.013	Neutral
Varity_R		0.029
gMVP		0.090
Mutation Taster		=99/1	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: rs541673443; hg19: chr19-57050392;