19-56550117-C-G

Position:

• chr19-56550117-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020828.2(ZFP28):​c.738C>G​(p.His246Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP28 NM_020828.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.112

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06934023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP28	NM_020828.2	c.738C>G	p.His246Gln	missense_variant	6/8	ENST00000301318.8	NP_065879.1
ZNF470-DT	XM_047439806.1	c.*11-2846G>C		intron_variant			XP_047295762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP28	ENST00000301318.8	c.738C>G	p.His246Gln	missense_variant	6/8	1	NM_020828.2	ENSP00000301318	P1
ZNF470-DT	ENST00000596587.2	n.370-2846G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.738C>G (p.H246Q) alteration is located in exon 6 (coding exon 6) of the ZFP28 gene. This alteration results from a C to G substitution at nucleotide position 738, causing the histidine (H) at amino acid position 246 to be replaced by a glutamine (Q). 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	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.52
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.20	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N;.
REVEL	Benign	0.072
Sift	Benign	0.59	T;.
Sift4G	Benign	0.62	T;T
Polyphen		0.0050	B;.
Vest4		0.15
MutPred		0.27		Loss of ubiquitination at K250 (P = 0.1231);Loss of ubiquitination at K250 (P = 0.1231);
MVP		0.20
MPC		0.20
ClinPred		0.035	T
GERP RS		1.2
Varity_R		0.052
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57061486;