3-75740820-G-C

Variant names:

• chr3-75740820-G-C
• rs1963442
• NM_001290208.3:c.277+456C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290208.3(ZNF717):​c.277+456C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 140,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000014 (0 hom., cov: 31)
• Consequence: ZNF717 NM_001290208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290208.3. 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
	ZNF717	NM_001290208.3	MANE Select	c.277+456C>G		intron	N/A	NP_001277137.1
	ZNF717	NM_001128223.3		c.277+456C>G		intron	N/A	NP_001121695.1
	ZNF717	NM_001290209.3		c.127+456C>G		intron	N/A	NP_001277138.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF717	ENST00000652011.2	MANE Select	c.277+456C>G		intron	N/A	ENSP00000498738.1
	LINC00960	ENST00000668145.2		n.744G>C		non_coding_transcript_exon	Exon 2 of 2
	ZNF717	ENST00000850935.1		c.379+456C>G		intron	N/A	ENSP00000521016.1

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 140226 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000715

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000143 AC: 2 AN: 140226 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 68504

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

African (AFR) AF: 0.0000257 AC: 1 AN: 38866

American (AMR) AF: 0.0000715 AC: 1 AN: 13994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3154

East Asian (EAS) AF: 0.00 AC: 0 AN: 4790

South Asian (SAS) AF: 0.00 AC: 0 AN: 4546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61922

Other (OTH) AF: 0.00 AC: 0 AN: 1914

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.23
PhyloP100		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1963442; hg19: chr3-75789971;