Variant chr19-34684259-A-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 ENST00000505242.6(ZNF302):c.222A>C(p.Glu74Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,558,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF302
ENST00000505242.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

ZNF302 (HGNC:13848): (zinc finger protein 302) This gene encodes a member of the zinc-finger protein family. The encoded protein contains seven C2H2-type zinc fingers and a KRAB domain, but its function has yet to be determined. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2014]

ZNF302 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=0.017365307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF302	NM_001289187.2 linkuse as main transcript	c.222A>C	p.Glu74Asp	missense_variant	5/5	ENST00000505242.6	NP_001276116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF302	ENST00000505242.6 linkuse as main transcript	c.222A>C	p.Glu74Asp	missense_variant	5/5	1	NM_001289187.2	ENSP00000421028	P4	Q9NR11-2

Frequencies

GnomAD3 genomes

AF:

0.000252

AC:

AN:

150674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00212

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:

0.00

Gnomad OTH

AF:

0.00194

GnomAD3 exomes

AF:

0.0000237

AC:

AN:

211046

Hom.:

AF XY:

0.0000260

AC XY:

AN XY:

115602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

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:

0.00

Gnomad OTH exome

AF:

0.000208

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1407740

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

698780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000539

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:

9.15e-7

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.000252

AC:

AN:

150794

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

73658

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00211

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00192

ExAC

AF:

0.0000330

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

Nov 06, 2023

The c.222A>C (p.E74D) alteration is located in exon 5 (coding exon 4) of the ZNF302 gene. This alteration results from a A to C substitution at nucleotide position 222, causing the glutamic acid (E) at amino acid position 74 to be replaced by an aspartic acid (D). 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

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;.;T;.;.;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.20

T;.;T;.;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.017

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.6

.;N;N;N;N;N

REVEL

Benign

0.023

Sift

Uncertain

0.015

.;D;D;D;D;T

Sift4G

Benign

0.11

T;T;D;T;T;T

Polyphen

0.59, 0.23

.;P;.;P;P;B

Vest4

0.076

MutPred

0.21

.;.;.;.;.;Gain of MoRF binding (P = 0.1264);

MVP

0.095

MPC

0.047

ClinPred

0.033

GERP RS

0.97

gMVP

0.028

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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