chr19-56549120-C-G

Variant names:

• chr19-56549120-C-G
• rs776198048
• NM_020828.2:c.686C>G

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.686C>G​(p.Pro229Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. P229L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: ZFP28 NM_020828.2 missense, splice_region
• Scores: Splicing: ADA: 0.00004053
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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]

ZNF470-DT (HGNC:55272): (ZNF470 divergent transcript)

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=0.06223491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.686C>G	p.Pro229Arg	missense_variant, splice_region_variant	Exon 5 of 8	ENST00000301318.8	NP_065879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.686C>G	p.Pro229Arg	missense_variant, splice_region_variant	Exon 5 of 8	1	NM_020828.2	ENSP00000301318.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1445180 Hom.: 0 Cov.: 32 AF XY: 0.00000279 AC XY: 2 AN XY: 717424

African (AFR) AF: 0.00 AC: 0 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 42194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 39140

South Asian (SAS) AF: 0.00 AC: 0 AN: 82876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5654

European-Non Finnish (NFE) AF: 0.00000453 AC: 5 AN: 1103962

Other (OTH) AF: 0.00 AC: 0 AN: 59710

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.0
DANN	Benign	0.25
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		-0.41
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.055
Sift	Benign	0.85	T;.
Sift4G	Benign	0.60	T;T
Polyphen		0.027	B;.
Vest4		0.21
MutPred		0.39		Loss of catalytic residue at Q228 (P = 0.1528);Loss of catalytic residue at Q228 (P = 0.1528);
MVP		0.17
MPC		0.19
ClinPred		0.029	T
GERP RS		-1.4
Varity_R		0.052
gMVP		0.12
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000041
dbscSNV1_RF	Benign	0.0
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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs776198048; hg19: chr19-57060489;