dbSNP rs1278962266: ZNF304:p.Thr52Ala (chr19-57353845-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020657.4(ZNF304):c.154A>G(p.Thr52Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,449,258 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T52S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ZNF304
NM_020657.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.705

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048950195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF304	NM_020657.4 link	c.154A>G	p.Thr52Ala	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>G	p.Thr52Ala	missense_variant	Exon 2 of 3	2	NM_020657.4	ENSP00000282286.4	Q9HCX3
ZNF304	ENST00000443917.6 link	c.154A>G	p.Thr52Ala	missense_variant	Exon 2 of 4	1		ENSP00000401642.2	E7EQD3
ZNF304	ENST00000598744.1 link	c.28A>G	p.Thr10Ala	missense_variant	Exon 3 of 4	1		ENSP00000470319.1	M0QZ59
ZNF304	ENST00000391705.7 link	c.154A>G	p.Thr52Ala	missense_variant	Exon 3 of 4	5		ENSP00000375586.3	Q9HCX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000345

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:

0.00000452

AC:

AN:

1105426

Other (OTH)

AF:

0.00

AC:

AN:

59808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0020

T;.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.63

T;T;T;.

M_CAP

Benign

0.0031

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.78

N;.;.;N

PhyloP100

0.70

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.53

N;N;.;N

REVEL

Benign

0.047

Sift

Benign

0.053

T;D;.;T

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.0

B;B;.;B

Vest4

0.080

MutPred

0.60

Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);

MVP

0.13

MPC

0.28

ClinPred

0.10

GERP RS

1.3

Varity_R

0.036

gMVP

0.10

Mutation Taster

=95/5

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

Computational scores

Splicing

Publications

Other links and lift over