19-56539028-G-A

Variant names:

• chr19-56539028-G-A
• rs1160217833
• NM_020828.2:c.10G>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.10G>A​(p.Ala4Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 1,435,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A4S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• 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=0.05237767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1
ZFP28	NM_001308440.2	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 7		NP_001295369.1
ZFP28	XM_011526463.4	c.182-597G>A		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4	c.-576G>A		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3
ZFP28	ENST00000591844.5	c.10G>A	p.Ala4Thr	missense_variant	Exon 1 of 7	1		ENSP00000468603.1
ZFP28	ENST00000589836.1	n.-102G>A		upstream_gene_variant		5		ENSP00000465853.1
ZFP28	ENST00000594386.1	n.-41G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151284 Hom.: 0 Cov.: 31

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: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000367 AC: 2 AN: 54526 AF XY: 0.0000658

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: 0.0000455

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000311 AC: 4 AN: 1284246 Hom.: 0 Cov.: 32 AF XY: 0.00000319 AC XY: 2 AN XY: 627680

African (AFR) AF: 0.00 AC: 0 AN: 25852

American (AMR) AF: 0.00 AC: 0 AN: 20932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19218

East Asian (EAS) AF: 0.00 AC: 0 AN: 32212

South Asian (SAS) AF: 0.00 AC: 0 AN: 64764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3620

European-Non Finnish (NFE) AF: 0.00000387 AC: 4 AN: 1033954

Other (OTH) AF: 0.00 AC: 0 AN: 53030

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151284 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2 AN XY: 73880

African (AFR) AF: 0.00 AC: 0 AN: 41174

American (AMR) AF: 0.00 AC: 0 AN: 15218

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67706

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;N
PhyloP100		-0.19
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.30	N;.
REVEL	Benign	0.010
Sift	Benign	0.20	T;.
Sift4G	Benign	0.39	T;T
Polyphen		0.027	B;.
Vest4		0.15
MutPred		0.16		Gain of glycosylation at A4 (P = 0.0215);Gain of glycosylation at A4 (P = 0.0215);
MVP		0.076
MPC		0.17
ClinPred		0.022	T
GERP RS		-0.95
PromoterAI		0.024	Neutral
Varity_R		0.029
gMVP		0.082
Mutation Taster		=99/1	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: rs1160217833; hg19: chr19-57050397;