Variant chr19-57356231-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020657.4(ZNF304):c.362T>C(p.Leu121Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,614,154 control chromosomes in the GnomAD database, including 1,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.043 ( 233 hom., cov: 33)

Exomes 𝑓: 0.038 ( 1613 hom. )

Consequence

ZNF304
NM_020657.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Variant links:

Genes affected

ZNF304 (HGNC:13505): (zinc finger protein 304) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein functions as a transcriptional repressor that recruits a corepressor complex to stimulate promoter hypermethylation and transcriptional silencing of target genes. Expression of this gene is upregulated in colorectal, ovarian and breast cancer, and this gene may promote cancer cell survival, growth and invasion. [provided by RefSeq, Jul 2016]

ZNF304 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004664302).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF304	NM_020657.4 linkuse as main transcript	c.362T>C	p.Leu121Pro	missense_variant	3/3	ENST00000282286.6	NP_065708.2	Q9HCX3Q2T9G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF304	ENST00000282286.6 linkuse as main transcript	c.362T>C	p.Leu121Pro	missense_variant	3/3	2	NM_020657.4	ENSP00000282286.4	Q9HCX3
ZNF304	ENST00000443917.6 linkuse as main transcript	c.503T>C	p.Leu168Pro	missense_variant	4/4	1		ENSP00000401642.2	E7EQD3
ZNF304	ENST00000598744.1 linkuse as main transcript	c.236T>C	p.Leu79Pro	missense_variant	4/4	1		ENSP00000470319.1	M0QZ59
ZNF304	ENST00000391705.7 linkuse as main transcript	c.362T>C	p.Leu121Pro	missense_variant	4/4	5		ENSP00000375586.3	Q9HCX3

Frequencies

GnomAD3 genomes

AF:

0.0432

AC:

6575

AN:

152164

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0788

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.0395

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0536

AC:

13459

AN:

251284

Hom.:

612

AF XY:

0.0524

AC XY:

7112

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.0322

Gnomad AMR exome

AF:

0.0807

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.197

Gnomad SAS exome

AF:

0.0554

Gnomad FIN exome

AF:

0.0395

Gnomad NFE exome

AF:

0.0299

Gnomad OTH exome

AF:

0.0432

GnomAD4 exome

AF:

0.0376

AC:

55022

AN:

1461872

Hom.:

1613

Cov.:

AF XY:

0.0382

AC XY:

27788

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0315

Gnomad4 AMR exome

AF:

0.0798

Gnomad4 ASJ exome

AF:

0.0319

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.0563

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.0295

Gnomad4 OTH exome

AF:

0.0440

GnomAD4 genome

AF:

0.0432

AC:

6582

AN:

152282

Hom.:

233

Cov.:

AF XY:

0.0464

AC XY:

3456

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.0788

Gnomad4 ASJ

AF:

0.0329

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.0658

Gnomad4 FIN

AF:

0.0395

Gnomad4 NFE

AF:

0.0301

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0358

Hom.:

372

Bravo

AF:

0.0449

TwinsUK

AF:

0.0286

AC:

106

ALSPAC

AF:

0.0275

AC:

106

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.0280

AC:

241

ExAC

AF:

0.0514

AC:

6236

Asia WGS

AF:

0.116

AC:

402

AN:

3478

EpiCase

AF:

0.0341

EpiControl

AF:

0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.10

DANN

Benign

0.19

DEOGEN2

Benign

0.0033

T;.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.13

T;T;T;.

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.;L

PrimateAI

Benign

0.21

PROVEAN

Benign

1.4

N;N;.;N

REVEL

Benign

0.022

Sift

Benign

0.22

T;T;.;T

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.039

MPC

0.46

ClinPred

0.00020

GERP RS

1.1

Varity_R

0.039

gMVP

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over