Variant 7-64978457-G-C 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.1114C>G(p.Gln372Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000633 in 1,612,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

ZNF117
NM_015852.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.50

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:

ERV3-1-ZNF117 (HGNC:):

ERV3-1-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=0.062168717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF117	NM_015852.5 linkuse as main transcript	c.1114C>G	p.Gln372Glu	missense_variant	4/4	ENST00000282869.11	NP_056936.2
ERV3-1-ZNF117	NM_001348050.2 linkuse as main transcript	c.1114C>G	p.Gln372Glu	missense_variant	4/4		NP_001334979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11 linkuse as main transcript	c.1114C>G	p.Gln372Glu	missense_variant	4/4	1	NM_015852.5	ENSP00000282869	P1
ZNF117	ENST00000620222.4 linkuse as main transcript	c.1114C>G	p.Gln372Glu	missense_variant	3/3	1		ENSP00000479944	P1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249188

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135196

show subpopulations

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:

0.00

Gnomad NFE exome

AF:

0.0000886

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461444

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727026

show subpopulations

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:

0.0000738

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73516

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000902

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000164

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

Jun 10, 2024

The c.1114C>G (p.Q372E) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a C to G substitution at nucleotide position 1114, causing the glutamine (Q) at amino acid position 372 to be replaced by a glutamic acid (E). 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

0.21

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.18

DANN

Benign

0.46

DEOGEN2

Benign

0.0026

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00094

LIST_S2

Benign

0.0057

.;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.0090

Sift

Benign

0.27

T;.

Sift4G

Benign

0.14

T;T

Polyphen

0.38

B;B

Vest4

0.041

MVP

0.19

MPC

0.015

ClinPred

0.048

GERP RS

0.068

Varity_R

0.059

gMVP

0.0041

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