chr19-56539059-C-A

Variant names:

• chr19-56539059-C-A
• rs2044166765
• NM_020828.2:c.41C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020828.2(ZFP28):​c.41C>A​(p.Pro14Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P14T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.192
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08762857).

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.41C>A	p.Pro14Gln	missense	Exon 1 of 8	NP_065879.1	Q8NHY6-1
	ZFP28	NM_001308440.2		c.41C>A	p.Pro14Gln	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.41C>A	p.Pro14Gln	missense	Exon 1 of 8	ENSP00000301318.3	Q8NHY6-1
	ZFP28	ENST00000591844.5	TSL:1	c.41C>A	p.Pro14Gln	missense	Exon 1 of 7	ENSP00000468603.1	Q8NHY6-2
	ZFP28	ENST00000955594.1		c.41C>A	p.Pro14Gln	missense	Exon 1 of 7	ENSP00000625653.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1352192 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 666024

African (AFR) AF: 0.00 AC: 0 AN: 28778

American (AMR) AF: 0.00 AC: 0 AN: 31106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24006

East Asian (EAS) AF: 0.00 AC: 0 AN: 33978

South Asian (SAS) AF: 0.00 AC: 0 AN: 76994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3944

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063450

Other (OTH) AF: 0.00 AC: 0 AN: 55942

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
PhyloP100		0.19
PromoterAI		0.032	Neutral
Varity_R		0.043
gMVP		0.12
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2044166765; hg19: chr19-57050428;