rs862708

Variant names:

• chr19-57356231-T-C
• rs862708
• NM_020657.4:c.362T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020657.4(ZNF304):​c.362T>C​(p.Leu121Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,614,154 control chromosomes in the GnomAD database, including 1,846 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.043 (233 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1613 hom.)
• Consequence: ZNF304 NM_020657.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 10 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004664302).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF304	NM_020657.4	MANE Select	c.362T>C	p.Leu121Pro	missense	Exon 3 of 3	NP_065708.2
	ZNF304	NM_001290318.2		c.503T>C	p.Leu168Pro	missense	Exon 4 of 4	NP_001277247.1
	ZNF304	NM_001290319.2		c.236T>C	p.Leu79Pro	missense	Exon 4 of 4	NP_001277248.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF304	ENST00000282286.6	TSL:2 MANE Select	c.362T>C	p.Leu121Pro	missense	Exon 3 of 3	ENSP00000282286.4
	ZNF304	ENST00000443917.6	TSL:1	c.503T>C	p.Leu168Pro	missense	Exon 4 of 4	ENSP00000401642.2
	ZNF304	ENST00000598744.1	TSL:1	c.236T>C	p.Leu79Pro	missense	Exon 4 of 4	ENSP00000470319.1

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6575 AN: 152164 Hom.: 235 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0359

GnomAD2 exomes AF: 0.0536 AC: 13459 AN: 251284 AF XY: 0.0524

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.0807

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.0395

Gnomad NFE exome AF: 0.0299

Gnomad OTH exome AF: 0.0432

GnomAD4 exome AF: 0.0376 AC: 55022 AN: 1461872 Hom.: 1613 Cov.: 33 AF XY: 0.0382 AC XY: 27788 AN XY: 727236

African (AFR) AF: 0.0315 AC: 1054 AN: 33480

American (AMR) AF: 0.0798 AC: 3570 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0319 AC: 834 AN: 26136

East Asian (EAS) AF: 0.177 AC: 7009 AN: 39700

South Asian (SAS) AF: 0.0563 AC: 4855 AN: 86258

European-Finnish (FIN) AF: 0.0370 AC: 1977 AN: 53420

Middle Eastern (MID) AF: 0.0371 AC: 214 AN: 5768

European-Non Finnish (NFE) AF: 0.0295 AC: 32850 AN: 1111992

Other (OTH) AF: 0.0440 AC: 2659 AN: 60396

GnomAD4 genome AF: 0.0432 AC: 6582 AN: 152282 Hom.: 233 Cov.: 33 AF XY: 0.0464 AC XY: 3456 AN XY: 74470

African (AFR) AF: 0.0327 AC: 1361 AN: 41566

American (AMR) AF: 0.0788 AC: 1205 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1004 AN: 5174

South Asian (SAS) AF: 0.0658 AC: 318 AN: 4830

European-Finnish (FIN) AF: 0.0395 AC: 419 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0301 AC: 2049 AN: 68018

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0360 Hom.: 685

Bravo AF: 0.0449

TwinsUK AF: 0.0286 AC: 106

ALSPAC AF: 0.0275 AC: 106

ESP6500AA AF: 0.0325 AC: 143

ESP6500EA AF: 0.0280 AC: 241

ExAC AF: 0.0514 AC: 6236

Asia WGS AF: 0.116 AC: 402 AN: 3478

EpiCase AF: 0.0341

EpiControl AF: 0.0327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.10
DANN	Benign	0.19
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.022
Sift	Benign	0.22	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.039
MPC		0.46
ClinPred		0.00020	T
GERP RS		1.1
Varity_R		0.039
gMVP		0.15
Mutation Taster		=99/1	polymorphism (auto)

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: rs862708; hg19: chr19-57867599; COSMIC: COSV56584420; COSMIC: COSV56584420;