rs193921040

Variant names:

• chr3-75738395-G-A
• NM_001290208.3:c.1228C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-75738395-G-A
• chr3-75738395-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 11/17 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: not found (cov: 48)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF717 NM_001290208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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]

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.1228C>T	p.Leu410Phe	missense_variant	Exon 5 of 5	ENST00000652011.2	NP_001277137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF717	ENST00000652011.2	c.1228C>T	p.Leu410Phe	missense_variant	Exon 5 of 5		NM_001290208.3	ENSP00000498738.1

Frequencies

GnomAD3 genomes Cov.: 48

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1386714 Hom.: 0 Cov.: 75 AF XY: 0.00000146 AC XY: 1 AN XY: 683954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000187

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Uncertain	1.0
Eigen	Benign	0.0083
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.92	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.047	D
Vest4		0.097
MVP		0.13
ClinPred		0.92	D
GERP RS		1.7
gMVP		0.0019

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-75787546;