dbSNP rs193921040: ZNF717:p.Leu410Phe (chr3-75738395-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001290208.3(ZNF717):c.1228C>T(p.Leu410Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,386,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L410V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 48)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF717
NM_001290208.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2183978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF717	NM_001290208.3 link	c.1228C>T	p.Leu410Phe	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>T	p.Leu410Phe	missense_variant	Exon 5 of 5		NM_001290208.3	ENSP00000498738.1		Q9BY31

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1386714

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683954

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

31266

American (AMR)

AF:

0.00

AC:

AN:

34868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24712

East Asian (EAS)

AF:

0.00

AC:

AN:

35134

South Asian (SAS)

AF:

0.00

AC:

AN:

78490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1070276

Other (OTH)

AF:

0.00

AC:

AN:

57248

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.029673), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.0083

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.60

M_CAP

Benign

0.0041

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.92

PhyloP100

1.1

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.047

Vest4

0.097

MVP

0.13

ClinPred

0.92

GERP RS

1.7

gMVP

0.0019

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over