5-178931501-C-A

Position:

• chr5-178931501-C-A

Variant summary

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

The NM_030613.4(ZFP2):​c.188C>A​(p.Thr63Lys) 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: ZFP2 NM_030613.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.77

Genes affected

ZFP2 (HGNC:26138): (ZFP2 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 located 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=0.056095243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP2	NM_030613.4	c.188C>A	p.Thr63Lys	missense_variant	5/5	ENST00000361362.7	NP_085116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP2	ENST00000361362.7	c.188C>A	p.Thr63Lys	missense_variant	5/5	1	NM_030613.4	ENSP00000354453	P1
ZFP2	ENST00000523286.1	c.188C>A	p.Thr63Lys	missense_variant	5/5	1		ENSP00000430531	P1
ZFP2	ENST00000520301.5	c.188C>A	p.Thr63Lys	missense_variant	4/4	5		ENSP00000430980	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

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

Sep 14, 2022

The c.188C>A (p.T63K) alteration is located in exon 5 (coding exon 1) of the ZFP2 gene. This alteration results from a C to A substitution at nucleotide position 188, causing the threonine (T) at amino acid position 63 to be replaced by a lysine (K). 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	0.078
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0020
DANN	Benign	0.42
DEOGEN2	Benign	0.022	T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00090	N
LIST_S2	Benign	0.0027	.;.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.010	N;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.99	T;T;T
Sift4G	Benign	0.92	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.093
MutPred		0.30		Gain of ubiquitination at T63 (P = 0.0155);Gain of ubiquitination at T63 (P = 0.0155);Gain of ubiquitination at T63 (P = 0.0155);
MVP		0.048
MPC		0.036
ClinPred		0.035	T
GERP RS		-7.8
Varity_R		0.035
gMVP		0.29

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: chr5-178358502;