chr3-44721166-C-T

Variant summary

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

The NM_001134442.3(ZNF502):​c.349C>T​(p.Arg117Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117H) has been classified as Likely benign.

Frequency

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

Consequence

ZNF502
NM_001134442.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.140
Variant links:
Genes affected
ZNF502 (HGNC:23718): (zinc finger protein 502) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation by host of viral process. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0732027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF502NM_001134442.3 linkc.349C>T p.Arg117Cys missense_variant Exon 3 of 3 ENST00000436624.7 NP_001127914.1 Q8TBZ5Q96K08

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF502ENST00000436624.7 linkc.349C>T p.Arg117Cys missense_variant Exon 3 of 3 2 NM_001134442.3 ENSP00000406469.2 Q8TBZ5
ZNF502ENST00000296091.8 linkc.349C>T p.Arg117Cys missense_variant Exon 4 of 4 1 ENSP00000296091.4 Q8TBZ5
ZNF502ENST00000449836.5 linkc.349C>T p.Arg117Cys missense_variant Exon 3 of 3 3 ENSP00000397390.1 Q8TBZ5
ZNF502ENST00000411443.1 linkc.349C>T p.Arg117Cys missense_variant Exon 3 of 3 3 ENSP00000401717.1 C9JLT3

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152166
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
250404
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135486
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000708
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461794
Hom.:
0
Cov.:
31
AF XY:
0.0000344
AC XY:
25
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152284
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000388
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 06, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.349C>T (p.R117C) alteration is located in exon 4 (coding exon 2) of the ZNF502 gene. This alteration results from a C to T substitution at nucleotide position 349, causing the arginine (R) at amino acid position 117 to be replaced by a cysteine (C). 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
0.097
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.0061
T;T;T;.
Eigen
Benign
-0.96
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.00090
N
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.073
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;N;.
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-2.1
N;N;N;D
REVEL
Benign
0.079
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.0
B;B;B;.
Vest4
0.16
MVP
0.085
MPC
0.25
ClinPred
0.17
T
GERP RS
0.41
Varity_R
0.15
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs148172622; hg19: chr3-44762658; API