chr3-44721257-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.440C>T​(p.Thr147Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,786 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 (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF502
NM_001134442.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.94
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]

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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=0.0872449).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF502NM_001134442.3 linkc.440C>T p.Thr147Ile 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.440C>T p.Thr147Ile missense_variant Exon 3 of 3 2 NM_001134442.3 ENSP00000406469.2 Q8TBZ5
ZNF502ENST00000296091.8 linkc.440C>T p.Thr147Ile missense_variant Exon 4 of 4 1 ENSP00000296091.4 Q8TBZ5
ZNF502ENST00000449836.5 linkc.440C>T p.Thr147Ile missense_variant Exon 3 of 3 3 ENSP00000397390.1 Q8TBZ5
ZNF502ENST00000411443.1 linkc.440C>T p.Thr147Ile missense_variant Exon 3 of 3 3 ENSP00000401717.1 C9JLT3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461786
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.440C>T (p.T147I) 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 440, causing the threonine (T) at amino acid position 147 to be replaced by an isoleucine (I). 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
0.071
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
5.3
DANN
Benign
0.93
DEOGEN2
Benign
0.0024
T;T;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.00071
N
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.087
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L;L;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.82
N;N;N;D
REVEL
Benign
0.077
Sift
Benign
0.26
T;T;T;D
Sift4G
Benign
0.18
T;T;T;D
Polyphen
0.0
B;B;B;.
Vest4
0.057
MutPred
0.29
Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);Gain of helix (P = 0.1736);
MVP
0.014
MPC
0.17
ClinPred
0.054
T
GERP RS
-0.30
Varity_R
0.039
gMVP
0.059

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1420980812; hg19: chr3-44762749; API