Variant 7-64979216-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015852.5(ZNF117):c.355T>C(p.Cys119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,609,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF117
NM_015852.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.181

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12570554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2 link	c.355T>C	p.Cys119Arg	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5 link	c.355T>C	p.Cys119Arg	missense_variant	4/4		NP_056936.2	Q03924

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF117	ENST00000282869.11 link	c.355T>C	p.Cys119Arg	missense_variant	4/4	1		ENSP00000282869.5		Q03924
ZNF117	ENST00000620222.4 link	c.355T>C	p.Cys119Arg	missense_variant	3/3	1				Q03924

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245780

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133214

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:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1457402

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

724710

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:

0.0000324

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000825

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.00

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

Nov 02, 2023

The c.355T>C (p.C119R) alteration is located in exon 4 (coding exon 2) of the ZNF117 gene. This alteration results from a T to C substitution at nucleotide position 355, causing the cysteine (C) at amino acid position 119 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.057

T;T;.

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.26

.;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.090

N;N;.

PROVEAN

Pathogenic

-8.6

D;.;.

REVEL

Benign

0.039

Sift

Benign

0.19

T;.;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.99

D;D;.

Vest4

0.013

MutPred

0.33

Gain of MoRF binding (P = 0.0043);Gain of MoRF binding (P = 0.0043);Gain of MoRF binding (P = 0.0043);

MVP

0.19

MPC

0.067

ClinPred

0.35

GERP RS

-3.0

Varity_R

0.36

gMVP

0.0035

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