Variant 5-178932074-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030613.4(ZFP2):c.761G>C(p.Ser254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZFP2
NM_030613.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.313

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]

ZFP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.057382733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP2	NM_030613.4 linkuse as main transcript	c.761G>C	p.Ser254Thr	missense_variant	5/5	ENST00000361362.7	NP_085116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZFP2	ENST00000361362.7 linkuse as main transcript	c.761G>C	p.Ser254Thr	missense_variant	5/5	1	NM_030613.4	ENSP00000354453	P1
ZFP2	ENST00000523286.1 linkuse as main transcript	c.761G>C	p.Ser254Thr	missense_variant	5/5	1		ENSP00000430531	P1
ZFP2	ENST00000520301.5 linkuse as main transcript	c.761G>C	p.Ser254Thr	missense_variant	4/4	5		ENSP00000430980	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251262

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.761G>C (p.S254T) alteration is located in exon 5 (coding exon 1) of the ZFP2 gene. This alteration results from a G to C substitution at nucleotide position 761, causing the serine (S) at amino acid position 254 to be replaced by a threonine (T). 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

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.044

T;T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.071

.;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.023

B;B;B

Vest4

0.15

MutPred

0.21

Loss of ubiquitination at K249 (P = 0.0755);Loss of ubiquitination at K249 (P = 0.0755);Loss of ubiquitination at K249 (P = 0.0755);

MVP

0.18

MPC

0.048

ClinPred

0.063

GERP RS

4.7

Varity_R

0.13

gMVP

0.025

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over