19-56539175-C-T

Variant names:

• chr19-56539175-C-T
• rs1018800777
• NM_020828.2:c.157C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020828.2(ZFP28):​c.157C>T​(p.Leu53Phe) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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: -0.389

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06240374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.157C>T	p.Leu53Phe	missense_variant	Exon 1 of 8	ENST00000301318.8	NP_065879.1
ZFP28	NM_001308440.2	c.157C>T	p.Leu53Phe	missense_variant	Exon 1 of 7		NP_001295369.1
ZFP28	XM_011526463.4	c.182-450C>T		intron_variant	Intron 1 of 7		XP_011524765.2
ZFP28	XM_011526462.4	c.-429C>T		upstream_gene_variant			XP_011524764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.157C>T	p.Leu53Phe	missense_variant	Exon 1 of 8	1	NM_020828.2	ENSP00000301318.3
ZFP28	ENST00000591844.5	c.157C>T	p.Leu53Phe	missense_variant	Exon 1 of 7	1		ENSP00000468603.1
ZFP28	ENST00000589836.1	n.46C>T		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000465853.1
ZFP28	ENST00000594386.1	n.107C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1450850 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 721510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157C>T (p.L53F) alteration is located in exon 1 (coding exon 1) of the ZFP28 gene. This alteration results from a C to T substitution at nucleotide position 157, causing the leucine (L) at amino acid position 53 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.014
Sift	Benign	0.12	T;.
Sift4G	Benign	0.22	T;D
Polyphen		0.12	B;.
Vest4		0.061
MutPred		0.13		Gain of phosphorylation at S55 (P = 0.2086);Gain of phosphorylation at S55 (P = 0.2086);
MVP		0.11
MPC		0.22
ClinPred		0.090	T
GERP RS		0.74
Varity_R		0.083
gMVP		0.076

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

Publications

LitVar

Other links and lift over

dbSNP: rs1018800777; hg19: chr19-57050544;