7-64978261-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000282869.11(ZNF117):​c.1310G>T​(p.Arg437Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,440,438 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000025 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNF117
ENST00000282869.11 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.949
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.038633913).
BP6
Variant 7-64978261-C-A is Benign according to our data. Variant chr7-64978261-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3193949.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF117NM_015852.5 linkuse as main transcriptc.1310G>T p.Arg437Ile missense_variant 4/4 ENST00000282869.11 NP_056936.2
ERV3-1-ZNF117NM_001348050.2 linkuse as main transcriptc.1310G>T p.Arg437Ile missense_variant 4/4 NP_001334979.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF117ENST00000282869.11 linkuse as main transcriptc.1310G>T p.Arg437Ile missense_variant 4/41 NM_015852.5 ENSP00000282869 P1
ZNF117ENST00000620222.4 linkuse as main transcriptc.1310G>T p.Arg437Ile missense_variant 3/31 ENSP00000479944 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
10
AN:
145086
Hom.:
0
Cov.:
34
FAILED QC
Gnomad AFR
AF:
0.000205
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000210
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000152
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000808
AC:
2
AN:
247618
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134390
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:
0.0000656
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000250
AC:
36
AN:
1440438
Hom.:
0
Cov.:
33
AF XY:
0.0000307
AC XY:
22
AN XY:
716356
show subpopulations
Gnomad4 AFR exome
AF:
0.000122
Gnomad4 AMR exome
AF:
0.0000229
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000246
Gnomad4 OTH exome
AF:
0.0000505
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000689
AC:
10
AN:
145218
Hom.:
0
Cov.:
34
AF XY:
0.0000987
AC XY:
7
AN XY:
70922
show subpopulations
Gnomad4 AFR
AF:
0.000204
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000210
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000152
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000826
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsFeb 27, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.0030
DANN
Benign
0.32
DEOGEN2
Benign
0.0048
T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0012
N
LIST_S2
Benign
0.29
.;T
M_CAP
Benign
0.00092
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.2
L;L
MutationTaster
Benign
0.94
D
PROVEAN
Benign
0.85
N;.
REVEL
Benign
0.092
Sift
Benign
0.39
T;.
Sift4G
Benign
0.22
T;T
Polyphen
0.0
B;B
Vest4
0.12
MVP
0.10
MPC
0.013
ClinPred
0.012
T
GERP RS
-2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.037
gMVP
0.016

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.

Other links and lift over

dbSNP: rs762844393; hg19: chr7-64438639; COSMIC: COSV51426140; COSMIC: COSV51426140; API