chr3-75741269-G-A

Variant names:

• chr3-75741269-G-A
• rs201879005
• NM_001290208.3:c.277+7C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001290208.3(ZNF717):​c.277+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 725,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (0 hom., cov: 29)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: ZNF717 NM_001290208.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001551
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400

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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-75741269-G-A is Benign according to our data. Variant chr3-75741269-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 770535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF717	NM_001290208.3	c.277+7C>T		splice_region_variant, intron_variant	Intron 4 of 4	ENST00000652011.2	NP_001277137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF717	ENST00000652011.2	c.277+7C>T		splice_region_variant, intron_variant	Intron 4 of 4		NM_001290208.3	ENSP00000498738.1

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 6101 AN: 71578 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0874

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0563

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.0891

GnomAD2 exomes AF: 0.00 AC: 0 AN: 45146 AF XY: 0.00

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: 0.0190 AC: 12409 AN: 653736 Hom.: 0 Cov.: 22 AF XY: 0.0198 AC XY: 6407 AN XY: 323874

Gnomad4 AFR exome AF: 0.0120 AC: 228 AN: 19072

Gnomad4 AMR exome AF: 0.0314 AC: 505 AN: 16106

Gnomad4 ASJ exome AF: 0.0291 AC: 363 AN: 12458

Gnomad4 EAS exome AF: 0.0209 AC: 462 AN: 22090

Gnomad4 SAS exome AF: 0.00853 AC: 404 AN: 47340

Gnomad4 FIN exome AF: 0.0221 AC: 625 AN: 28240

Gnomad4 NFE exome AF: 0.0188 AC: 9011 AN: 478402

Gnomad4 Remaining exome AF: 0.0277 AC: 752 AN: 27158

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0851 AC: 6102 AN: 71666 Hom.: 0 Cov.: 29 AF XY: 0.0796 AC XY: 2834 AN XY: 35622

Gnomad4 AFR AF: 0.0431 AC: 0.0430849 AN: 0.0430849

Gnomad4 AMR AF: 0.103 AC: 0.102545 AN: 0.102545

Gnomad4 ASJ AF: 0.0874 AC: 0.0874352 AN: 0.0874352

Gnomad4 EAS AF: 0.0438 AC: 0.0438163 AN: 0.0438163

Gnomad4 SAS AF: 0.0510 AC: 0.0510285 AN: 0.0510285

Gnomad4 FIN AF: 0.0563 AC: 0.0563089 AN: 0.0563089

Gnomad4 NFE AF: 0.131 AC: 0.130761 AN: 0.130761

Gnomad4 OTH AF: 0.0876 AC: 0.0876289 AN: 0.0876289

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.60
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.026
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

LitVar

Other links and lift over

dbSNP: rs201879005; hg19: chr3-75790420;