rs193920881

Variant names:

• chr19-57357269-T-A
• rs193920881
• NM_020657.4:c.1400T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-57357269-T-A
• chr19-57357269-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020657.4(ZNF304):​c.1400T>A​(p.Ile467Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF304 NM_020657.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.683
• Publications: 0 publications found

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

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=0.06635198).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020657.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF304	NM_020657.4	MANE Select	c.1400T>A	p.Ile467Lys	missense	Exon 3 of 3	NP_065708.2	Q9HCX3
	ZNF304	NM_001290318.2		c.1541T>A	p.Ile514Lys	missense	Exon 4 of 4	NP_001277247.1	E7EQD3
	ZNF304	NM_001290319.2		c.1274T>A	p.Ile425Lys	missense	Exon 4 of 4	NP_001277248.1	M0QZ59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF304	ENST00000282286.6	TSL:2 MANE Select	c.1400T>A	p.Ile467Lys	missense	Exon 3 of 3	ENSP00000282286.4	Q9HCX3
	ZNF304	ENST00000443917.6	TSL:1	c.1541T>A	p.Ile514Lys	missense	Exon 4 of 4	ENSP00000401642.2	E7EQD3
	ZNF304	ENST00000598744.1	TSL:1	c.1274T>A	p.Ile425Lys	missense	Exon 4 of 4	ENSP00000470319.1	M0QZ59

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 727234

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-0.68
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	3.2	N
REVEL	Benign	0.072
Sift	Benign	0.47	T
Sift4G	Benign	0.33	T
Polyphen		0.0090	B
Vest4		0.33
MutPred		0.58		Gain of disorder (P = 0.013)
MVP		0.25
MPC		0.62
ClinPred		0.097	T
GERP RS		0.47
Varity_R		0.061
gMVP		0.36
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs193920881; hg19: chr19-57868637;