chr19-56549116-C-T

Variant names:

• chr19-56549116-C-T
• rs778841670
• NM_020828.2:c.682C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020828.2(ZFP28):​c.682C>T​(p.Gln228*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,450,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: ZFP28 NM_020828.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.682C>T	p.Gln228*	stop_gained	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.682C>T	p.Gln228*	stop_gained	Exon 5 of 8	1	NM_020828.2	ENSP00000301318.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240396 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: 0.00000907

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000241 AC: 35 AN: 1450434 Hom.: 0 Cov.: 32 AF XY: 0.0000236 AC XY: 17 AN XY: 720516

African (AFR) AF: 0.00 AC: 0 AN: 33080

American (AMR) AF: 0.00 AC: 0 AN: 42922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 39392

South Asian (SAS) AF: 0.00 AC: 0 AN: 83596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.0000316 AC: 35 AN: 1106804

Other (OTH) AF: 0.00 AC: 0 AN: 59966

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	-0.0062
FATHMM_MKL	Benign	0.24	N
PhyloP100		0.78
Vest4		0.064
GERP RS		3.2
Mutation Taster		=53/147	disease causing (fs/PTC)

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: rs778841670; hg19: chr19-57060485;