chr19-57353845-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020657.4(ZNF304):c.154A>T(p.Thr52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,601,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF304
NM_020657.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.705

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014685571).

BP6

Variant 19-57353845-A-T is Benign according to our data. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-57353845-A-T is described in CliVar as Likely_benign. Clinvar id is 2249030.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF304	NM_020657.4 link	c.154A>T	p.Thr52Ser	missense_variant	Exon 2 of 3	ENST00000282286.6	NP_065708.2	Q9HCX3Q2T9G7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF304	ENST00000282286.6 link	c.154A>T	p.Thr52Ser	missense_variant	Exon 2 of 3	2	NM_020657.4	ENSP00000282286.4	Q9HCX3
ZNF304	ENST00000443917.6 link	c.154A>T	p.Thr52Ser	missense_variant	Exon 2 of 4	1		ENSP00000401642.2	E7EQD3
ZNF304	ENST00000598744.1 link	c.28A>T	p.Thr10Ser	missense_variant	Exon 3 of 4	1		ENSP00000470319.1	M0QZ59
ZNF304	ENST00000391705.7 link	c.154A>T	p.Thr52Ser	missense_variant	Exon 3 of 4	5		ENSP00000375586.3	Q9HCX3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1449258

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720304

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

43086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25332

East Asian (EAS)

AF:

0.00

AC:

AN:

39512

South Asian (SAS)

AF:

0.00

AC:

AN:

84204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105426

Other (OTH)

AF:

0.0000334

AC:

AN:

59808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 14, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.5

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0010

T;.;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.60

T;T;T;.

M_CAP

Benign

0.0045

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-3.4

N;.;.;N

PhyloP100

0.70

PrimateAI

Benign

0.31

PROVEAN

Benign

1.7

N;N;.;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.073

MutPred

0.62

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);

MVP

0.14

MPC

0.26

ClinPred

0.022

GERP RS

1.3

Varity_R

0.039

gMVP

0.080

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over