chr1-26170093-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_015871.5(ZNF593):c.110C>T(p.Pro37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,419,224 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: 34)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
ZNF593
NM_015871.5 missense
NM_015871.5 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 1.67
Genes affected
ZNF593 (HGNC:30943): (zinc finger protein 593) Enables zinc ion binding activity. Involved in negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding activity and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [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=0.17943129).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF593 | NM_015871.5 | c.110C>T | p.Pro37Leu | missense_variant | 1/3 | ENST00000374266.7 | |
ZNF593OS | NM_001395468.1 | c.*539G>A | 3_prime_UTR_variant | 4/4 | ENST00000433939.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF593 | ENST00000374266.7 | c.110C>T | p.Pro37Leu | missense_variant | 1/3 | 1 | NM_015871.5 | P1 | |
ZNF593OS | ENST00000433939.7 | c.*539G>A | 3_prime_UTR_variant | 4/4 | 3 | NM_001395468.1 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
GnomAD4 exome AF: 0.00000352 AC: 5AN: 1419224Hom.: 0 Cov.: 33 AF XY: 0.00000569 AC XY: 4AN XY: 702674
GnomAD4 exome
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AC:
5
AN:
1419224
Hom.:
Cov.:
33
AF XY:
AC XY:
4
AN XY:
702674
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
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 | Mar 11, 2024 | The c.110C>T (p.P37L) alteration is located in exon 1 (coding exon 1) of the ZNF593 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0678);Gain of MoRF binding (P = 0.0678);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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