chr5-178931720-G-A

Position:

• chr5-178931720-G-A

Variant summary

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

The NM_030613.4(ZFP2):​c.407G>A​(p.Gly136Glu) 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. 12/21 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: 0.439

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 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=0.1330533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP2	NM_030613.4	c.407G>A	p.Gly136Glu	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.407G>A	p.Gly136Glu	missense_variant	5/5	1	NM_030613.4	ENSP00000354453	P1
ZFP2	ENST00000523286.1	c.407G>A	p.Gly136Glu	missense_variant	5/5	1		ENSP00000430531	P1
ZFP2	ENST00000520301.5	c.407G>A	p.Gly136Glu	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

Jan 03, 2024

The c.407G>A (p.G136E) alteration is located in exon 5 (coding exon 1) of the ZFP2 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the glycine (G) at amino acid position 136 to be replaced by a glutamic acid (E). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.54	.;.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L
MutationTaster	Benign	0.92	N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Benign	0.055
Sift	Benign	0.049	D;D;D
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.34	B;B;B
Vest4		0.18
MutPred		0.66		Gain of catalytic residue at G136 (P = 0.0494);Gain of catalytic residue at G136 (P = 0.0494);Gain of catalytic residue at G136 (P = 0.0494);
MVP		0.29
MPC		0.038
ClinPred		0.20	T
GERP RS		1.9
Varity_R		0.27
gMVP		0.042

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: chr5-178358721; COSMIC: COSV63726501; COSMIC: COSV63726501;