chr5-178932035-C-G

Variant summary

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

The NM_030613.4(ZFP2):ā€‹c.722C>Gā€‹(p.Pro241Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

ZFP2
NM_030613.4 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFP2NM_030613.4 linkuse as main transcriptc.722C>G p.Pro241Arg missense_variant 5/5 ENST00000361362.7 NP_085116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFP2ENST00000361362.7 linkuse as main transcriptc.722C>G p.Pro241Arg missense_variant 5/51 NM_030613.4 ENSP00000354453 P1
ZFP2ENST00000523286.1 linkuse as main transcriptc.722C>G p.Pro241Arg missense_variant 5/51 ENSP00000430531 P1
ZFP2ENST00000520301.5 linkuse as main transcriptc.722C>G p.Pro241Arg missense_variant 4/45 ENSP00000430980 P1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152094
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251070
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135714
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461756
Hom.:
0
Cov.:
37
AF XY:
0.00000413
AC XY:
3
AN XY:
727176
show subpopulations
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:
0.00000630
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152094
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 02, 2021The c.722C>G (p.P241R) alteration is located in exon 5 (coding exon 1) of the ZFP2 gene. This alteration results from a C to G substitution at nucleotide position 722, causing the proline (P) at amino acid position 241 to be replaced by an arginine (R). 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
Pathogenic
0.91
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;T;T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.24
.;.;T
M_CAP
Benign
0.0081
T
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-9.0
D;D;D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.56
MVP
0.44
MPC
0.25
ClinPred
0.96
D
GERP RS
4.9
Varity_R
0.66
gMVP
0.057

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143860506; hg19: chr5-178359036; API