19-57353788-G-C

Position:

• chr19-57353788-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020657.4(ZNF304):​c.97G>C​(p.Glu33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF304 NM_020657.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.110

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]

ACMG classification

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=0.09701857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF304	NM_020657.4	c.97G>C	p.Glu33Gln	missense_variant	2/3	ENST00000282286.6	NP_065708.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF304	ENST00000282286.6	c.97G>C	p.Glu33Gln	missense_variant	2/3	2	NM_020657.4	ENSP00000282286.4
ZNF304	ENST00000443917.6	c.97G>C	p.Glu33Gln	missense_variant	2/4	1		ENSP00000401642.2
ZNF304	ENST00000598744	c.-30G>C		5_prime_UTR_variant	3/4	1		ENSP00000470319.1
ZNF304	ENST00000391705.7	c.97G>C	p.Glu33Gln	missense_variant	3/4	5		ENSP00000375586.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

The c.97G>C (p.E33Q) alteration is located in exon 2 (coding exon 2) of the ZNF304 gene. This alteration results from a G to C substitution at nucleotide position 97, causing the glutamic acid (E) at amino acid position 33 to be replaced by a glutamine (Q). 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	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T;.;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.25	T;T;.
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.077
Sift	Uncertain	0.014	D;D;D
Sift4G	Uncertain	0.023	D;D;D
Polyphen		0.030	B;B;B
Vest4		0.26
MutPred		0.48		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.36
MPC		0.83
ClinPred		0.31	T
GERP RS		-0.057
Varity_R		0.085
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-57865156;