NM_020828.2:c.41C>G

Variant names:

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

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>G​(p.Pro14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 1,503,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P14Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.084340155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.41C>G	p.Pro14Arg	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1
ZFP28	NM_001308440.2	c.41C>G	p.Pro14Arg	missense_variant	Exon 1 of 7		NP_001295369.1
ZFP28	XM_011526463.4	c.182-566C>G		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4	c.-545C>G		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.41C>G	p.Pro14Arg	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3
ZFP28	ENST00000591844.5	c.41C>G	p.Pro14Arg	missense_variant	Exon 1 of 7	1		ENSP00000468603.1
ZFP28	ENST00000589836.1	n.-71C>G		upstream_gene_variant		5		ENSP00000465853.1
ZFP28	ENST00000594386.1	n.-10C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151176 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000296 AC: 4 AN: 1352192 Hom.: 0 Cov.: 33 AF XY: 0.00000450 AC XY: 3 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: 0.00000376 AC: 4 AN: 1063450

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

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151176 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73798

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41114

American (AMR) AF: 0.00 AC: 0 AN: 15224

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5052

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67708

Other (OTH) AF: 0.00 AC: 0 AN: 2068

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.5
DANN	Benign	0.94
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N;N
PhyloP100		0.19
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.65	N;.
REVEL	Benign	0.012
Sift	Benign	0.080	T;.
Sift4G	Benign	0.17	T;D
Polyphen		0.047	B;.
Vest4		0.13
MutPred		0.26		Gain of MoRF binding (P = 0.011);Gain of MoRF binding (P = 0.011);
MVP		0.19
MPC		0.21
ClinPred		0.071	T
GERP RS		1.1
PromoterAI		0.0080	Neutral
Varity_R		0.042
gMVP		0.10
Mutation Taster		=92/8	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: rs2044166765; hg19: chr19-57050428;