Variant 7-64978147-C-T 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.1424G>A(p.Cys475Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000207 in 1,611,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

ZNF117
NM_015852.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 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=0.1600419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERV3-1-ZNF117	NM_001348050.2 linkuse as main transcript	c.1424G>A	p.Cys475Tyr	missense_variant	4/4		NP_001334979.1
ZNF117	NM_015852.5 linkuse as main transcript	c.1424G>A	p.Cys475Tyr	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.1424G>A	p.Cys475Tyr	missense_variant	4/4	1		ENSP00000282869.5		Q03924
ZNF117	ENST00000620222.4 linkuse as main transcript	c.1424G>A	p.Cys475Tyr	missense_variant	3/3	1				Q03924

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000138

AC:

AN:

246498

Hom.:

AF XY:

0.000135

AC XY:

AN XY:

133744

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:

0.000238

Gnomad NFE exome

AF:

0.000251

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000218

AC:

318

AN:

1459024

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

142

AN XY:

725794

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:

0.000133

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000481

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:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000896

Hom.:

Bravo

AF:

0.000121

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.000132

AC:

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

Oct 08, 2024

The c.1424G>A (p.C475Y) 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 1424, causing the cysteine (C) at amino acid position 475 to be replaced by a tyrosine (Y). 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

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.079

.;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.16

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Pathogenic

3.9

H;H

PROVEAN

Pathogenic

-6.3

D;.

REVEL

Uncertain

0.32

Sift

Benign

0.072

T;.

Sift4G

Uncertain

0.023

D;D

Polyphen

0.80

P;P

Vest4

0.17

MVP

0.83

MPC

0.015

ClinPred

0.34

GERP RS

1.1

Varity_R

0.18

gMVP

0.051

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