Variant 19-57356375-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020657.4(ZNF304):c.506G>A(p.Cys169Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF304
NM_020657.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.129

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 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=0.20611775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF304	NM_020657.4 linkuse as main transcript	c.506G>A	p.Cys169Tyr	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.506G>A	p.Cys169Tyr	missense_variant	3/3	2	NM_020657.4	ENSP00000282286.4	Q9HCX3
ZNF304	ENST00000443917.6 linkuse as main transcript	c.647G>A	p.Cys216Tyr	missense_variant	4/4	1		ENSP00000401642.2	E7EQD3
ZNF304	ENST00000598744.1 linkuse as main transcript	c.380G>A	p.Cys127Tyr	missense_variant	4/4	1		ENSP00000470319.1	M0QZ59
ZNF304	ENST00000391705.7 linkuse as main transcript	c.506G>A	p.Cys169Tyr	missense_variant	4/4	5		ENSP00000375586.3	Q9HCX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251366

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135840

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:

0.00000410

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 01, 2024

The c.506G>A (p.C169Y) alteration is located in exon 3 (coding exon 3) of the ZNF304 gene. This alteration results from a G to A substitution at nucleotide position 506, causing the cysteine (C) at amino acid position 169 to be replaced by a tyrosine (Y). 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

0.077

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.9

DANN

Benign

0.67

DEOGEN2

Benign

0.11

T;.;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.11

T;T;T;.

M_CAP

Benign

0.0020

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.3

M;.;.;M

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-5.2

D;D;.;D

REVEL

Benign

0.042

Sift

Benign

0.21

T;T;.;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0060

B;B;.;B

Vest4

0.15

MutPred

0.67

.;Gain of phosphorylation at C216 (P = 0.0457);.;.;

MVP

0.25

MPC

0.49

ClinPred

0.20

GERP RS

1.4

Varity_R

0.097

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over