NM_001290208.3:c.1228C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290208.3(ZNF717):c.1228C>G(p.Leu410Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,538,504 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.034 ( 40 hom., cov: 48)

Exomes 𝑓: 0.030 ( 286 hom. )

Consequence

ZNF717
NM_001290208.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.13

Publications

8 publications found

Variant links:

Genes affected

ZNF717 (HGNC:29448): (zinc finger protein 717) This gene encodes a Kruppel-associated box (KRAB) zinc-finger protein, which belongs to a large group of transcriptional regulators in mammals. These proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation and apoptosis, and in regulating viral replication and transcription. A pseudogene of this gene was identified on chromosome 1. [provided by RefSeq, May 2016]

ZNF717 links:

LINC00960 (HGNC:48710): (long intergenic non-protein coding RNA 960)

LINC00960 links:

MIR4273 (HGNC:38339): (microRNA 4273) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4273 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0046102107).

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF717	NM_001290208.3 link	c.1228C>G	p.Leu410Val	missense_variant	Exon 5 of 5	ENST00000652011.2	NP_001277137.1	Q9BY31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF717	ENST00000652011.2 link	c.1228C>G	p.Leu410Val	missense_variant	Exon 5 of 5		NM_001290208.3	ENSP00000498738.1		Q9BY31

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5175

AN:

151752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.0232

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0592

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0264

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

27922

AF XY:

0.0000702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0304

AC:

42103

AN:

1386634

Hom.:

286

Cov.:

AF XY:

0.0313

AC XY:

21395

AN XY:

683928

show subpopulations

African (AFR)

AF:

0.0585

AC:

1829

AN:

31266

American (AMR)

AF:

0.0189

AC:

660

AN:

34868

Ashkenazi Jewish (ASJ)

AF:

0.0251

AC:

620

AN:

24712

East Asian (EAS)

AF:

0.000171

AC:

AN:

35134

South Asian (SAS)

AF:

0.0677

AC:

5311

AN:

78486

European-Finnish (FIN)

AF:

0.0182

AC:

894

AN:

49062

Middle Eastern (MID)

AF:

0.0481

AC:

272

AN:

5654

European-Non Finnish (NFE)

AF:

0.0287

AC:

30706

AN:

1070206

Other (OTH)

AF:

0.0315

AC:

1805

AN:

57246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

2367

4734

7100

9467

11834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1202

2404

3606

4808

6010

<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

AF:

0.0341

AC:

5174

AN:

151870

Hom.:

Cov.:

AF XY:

0.0335

AC XY:

2484

AN XY:

74252

show subpopulations

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

African (AFR)

AF:

0.0575

AC:

2380

AN:

41408

American (AMR)

AF:

0.0246

AC:

376

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3468

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0588

AC:

283

AN:

4814

European-Finnish (FIN)

AF:

0.0148

AC:

157

AN:

10606

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0268

AC:

1817

AN:

67832

Other (OTH)

AF:

0.0261

AC:

AN:

2106

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

215

430

644

859

1074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0360

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Prostate cancer

Uncertain:1

Science for Life laboratory, Karolinska Institutet

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.088

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.83

M_CAP

Benign

0.0037

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.86

PhyloP100

1.1

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.23

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Vest4

0.11

MVP

0.12

ClinPred

0.38

GERP RS

1.7

gMVP

0.0014

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over