19-43846954-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001297752.2(ZNF283):c.-65C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,344,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000037 ( 0 hom. )
Consequence
ZNF283
NM_001297752.2 5_prime_UTR_premature_start_codon_gain
NM_001297752.2 5_prime_UTR_premature_start_codon_gain
Scores
2
17
Clinical Significance
Conservation
PhyloP100: -0.0860
Genes affected
ZNF283 (HGNC:13077): (zinc finger protein 283) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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=0.110592514).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF283 | NM_181845.2 | c.353C>T | p.Thr118Met | missense_variant | 7/7 | ENST00000618787.5 | NP_862828.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF283 | ENST00000618787.5 | c.353C>T | p.Thr118Met | missense_variant | 7/7 | 2 | NM_181845.2 | ENSP00000484852.1 | ||
ZNF283 | ENST00000324461.9 | c.353C>T | p.Thr118Met | missense_variant | 4/4 | 1 | ENSP00000327314.7 | |||
ZNF283 | ENST00000650832.1 | c.245C>T | p.Thr82Met | missense_variant | 7/7 | ENSP00000498705.1 | ||||
ZNF283 | ENST00000588797.6 | c.118C>T | p.Arg40Cys | missense_variant | 6/6 | 2 | ENSP00000468708.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
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31
GnomAD3 exomes AF: 0.00000990 AC: 2AN: 201934Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 109716
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GnomAD4 exome AF: 0.00000372 AC: 5AN: 1344766Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 665196
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GnomAD4 genome Cov.: 31
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31
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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 | May 03, 2023 | The c.353C>T (p.T118M) alteration is located in exon 7 (coding exon 4) of the ZNF283 gene. This alteration results from a C to T substitution at nucleotide position 353, causing the threonine (T) at amino acid position 118 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP
MPC
0.85
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at