3-75741362-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001290208.3(ZNF717):c.191A>G(p.Tyr64Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,515,380 control chromosomes in the GnomAD database, including 531,993 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (53023 hom., cov: 38)
  • Exomes 𝑓: 0.84 (478970 hom.)
• Consequence: ZNF717 NM_001290208.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.90

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067239106).
• BP6: Variant 3-75741362-T-C is Benign according to our data. Variant chr3-75741362-T-C is described in ClinVar as [Benign]. Clinvar id is 769608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF717	NM_001290208.3	c.191A>G	p.Tyr64Cys	missense_variant	4/5	ENST00000652011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF717	ENST00000652011.2	c.191A>G	p.Tyr64Cys	missense_variant	4/5		NM_001290208.3	P1
LINC00960	ENST00000668145.1	n.1240T>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.846 AC: 127974 AN: 151218 Hom.: 52968 Cov.: 38

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.867

GnomAD3 exomes AF: 0.0000437 AC: 2 AN: 45734 Hom.: 0 AF XY: 0.0000414 AC XY: 1 AN XY: 24162

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000342

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.844 AC: 1151530 AN: 1364046 Hom.: 478970 Cov.: 29 AF XY: 0.845 AC XY: 569602 AN XY: 673924

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.857

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.807

Gnomad4 NFE exome AF: 0.841

Gnomad4 OTH exome AF: 0.855

GnomAD4 genome AF: 0.846 AC: 128085 AN: 151334 Hom.: 53023 Cov.: 38 AF XY: 0.846 AC XY: 62615 AN XY: 74002

Gnomad4 AFR AF: 0.839

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.868

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.867

Alfa AF: 0.837 Hom.: 9561

ExAC AF: 0.0109 AC: 107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.74
Dann	Benign	0.62
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.015	T;T;T;T
M_CAP	Benign	0.00064	T
MetaRNN	Benign	0.0067	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.47	T
PROVEAN	Benign	9.2	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.64	T;T;.;.
Vest4		0.082
ClinPred		0.042	T
GERP RS		-2.6
gMVP		0.0067

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

LitVar

Other links and lift over

dbSNP: rs2918519; hg19: chr3-75790513; COSMIC: COSV68862300; COSMIC: COSV68862300;