rs3746414

Variant names:

• chr20-52152840-C-T
• rs3746414
• NM_018197.3:c.1352G>A

Variant summary

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

The NM_018197.3(ZFP64):​c.1352G>A​(p.Ser451Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,018 control chromosomes in the GnomAD database, including 37,715 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 0.20 (3227 hom., cov: 33)
  • Exomes 𝑓: 0.21 (34488 hom.)
• Consequence: ZFP64 NM_018197.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09
• Publications: 23 publications found

Genes affected

ZFP64 (HGNC:15940): (ZFP64 zinc finger protein) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in positive regulation of cytokine production and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of mRNA splicing, via spliceosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025477111).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018197.3. 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
	ZFP64	NM_018197.3	MANE Select	c.1352G>A	p.Ser451Asn	missense	Exon 6 of 6	NP_060667.2
	ZFP64	NM_199426.2		c.1346G>A	p.Ser449Asn	missense	Exon 6 of 6	NP_955458.1	Q9NTW7-4
	ZFP64	NM_022088.5		c.1190G>A	p.Ser397Asn	missense	Exon 5 of 5	NP_071371.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP64	ENST00000216923.5	TSL:1 MANE Select	c.1352G>A	p.Ser451Asn	missense	Exon 6 of 6	ENSP00000216923.4	Q9NTW7-5
	ZFP64	ENST00000371515.8	TSL:1	c.1346G>A	p.Ser449Asn	missense	Exon 6 of 6	ENSP00000360570.4	Q9NTW7-4
	ZFP64	ENST00000361387.6	TSL:1	c.763+7283G>A		intron	N/A	ENSP00000355179.2	Q9NTW7-1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30281 AN: 152086 Hom.: 3223 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.221 AC: 55411 AN: 250664 AF XY: 0.216

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0806

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.213 AC: 310944 AN: 1461814 Hom.: 34488 Cov.: 35 AF XY: 0.212 AC XY: 153964 AN XY: 727202

African (AFR) AF: 0.154 AC: 5145 AN: 33478

American (AMR) AF: 0.340 AC: 15187 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 4682 AN: 26132

East Asian (EAS) AF: 0.110 AC: 4363 AN: 39698

South Asian (SAS) AF: 0.182 AC: 15695 AN: 86258

European-Finnish (FIN) AF: 0.309 AC: 16504 AN: 53364

Middle Eastern (MID) AF: 0.117 AC: 675 AN: 5768

European-Non Finnish (NFE) AF: 0.213 AC: 237014 AN: 1111998

Other (OTH) AF: 0.193 AC: 11679 AN: 60396

GnomAD4 genome AF: 0.199 AC: 30316 AN: 152204 Hom.: 3227 Cov.: 33 AF XY: 0.204 AC XY: 15194 AN XY: 74412

African (AFR) AF: 0.152 AC: 6313 AN: 41560

American (AMR) AF: 0.261 AC: 3992 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3464

East Asian (EAS) AF: 0.0841 AC: 435 AN: 5170

South Asian (SAS) AF: 0.185 AC: 894 AN: 4828

European-Finnish (FIN) AF: 0.301 AC: 3181 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14341 AN: 67994

Other (OTH) AF: 0.189 AC: 400 AN: 2112

Alfa AF: 0.202 Hom.: 14255

Bravo AF: 0.196

TwinsUK AF: 0.204 AC: 757

ALSPAC AF: 0.196 AC: 756

ESP6500AA AF: 0.153 AC: 675

ESP6500EA AF: 0.217 AC: 1863

ExAC AF: 0.217 AC: 26317

Asia WGS AF: 0.138 AC: 480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0030
DANN	Benign	0.73
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		-4.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.12
Sift	Benign	0.85	T
Sift4G	Benign	0.86	T
Polyphen		0.0010	B
Vest4		0.033
MPC		0.55
ClinPred		0.0099	T
GERP RS		-11
Varity_R		0.026
gMVP		0.14
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: rs3746414; hg19: chr20-50769379; COSMIC: COSV53799554;