Variant 7-64978808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015852.5(ZNF117):c.763G>A(p.Gly255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

ZNF117
NM_015852.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680

Variant links:

Genes affected

ZNF117 (HGNC:12897): (zinc finger protein 117) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Readthrough transcription occurs between this gene and the upstream endogenous retrovirus group 3 member 1 (ERV3-1) locus, and may result in additional transcript variants encoding the zinc finger protein. [provided by RefSeq, Jan 2017]

ZNF117 links:

ZNF117 (HGNC:):

ZNF117 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03442663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2 linkuse as main transcript	c.763G>A	p.Gly255Ser	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5 linkuse as main transcript	c.763G>A	p.Gly255Ser	missense_variant	4/4		NP_056936.2	Q03924

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11 linkuse as main transcript	c.763G>A	p.Gly255Ser	missense_variant	4/4	1		ENSP00000282869.5		Q03924
ZNF117	ENST00000620222.4 linkuse as main transcript	c.763G>A	p.Gly255Ser	missense_variant	3/3	1				Q03924

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000525

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:

0.0000883

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000192

AC:

AN:

250090

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.000940

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000186

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000197

AC:

288

AN:

1461314

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

137

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000276

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000895

Hom.:

Bravo

AF:

0.000314

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.763G>A (p.G255S) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a G to A substitution at nucleotide position 763, causing the glycine (G) at amino acid position 255 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.14

.;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;.

PROVEAN

Pathogenic

-5.4

D;.;.

REVEL

Benign

0.040

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.014

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.091

MVP

0.23

MPC

0.091

ClinPred

0.18

GERP RS

1.2

Varity_R

0.37

gMVP

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over