chr19-30445004-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014717.3(ZNF536):c.1442C>T(p.Pro481Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,611,258 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: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
ZNF536
NM_014717.3 missense
NM_014717.3 missense
Scores
4
11
Clinical Significance
Conservation
PhyloP100: 3.99
Genes affected
ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.14800519).
BS2
High AC in GnomAdExome4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF536 | NM_014717.3 | c.1442C>T | p.Pro481Leu | missense_variant | 2/5 | ENST00000355537.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF536 | ENST00000355537.4 | c.1442C>T | p.Pro481Leu | missense_variant | 2/5 | 1 | NM_014717.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248008Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134580
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GnomAD4 exome AF: 0.0000158 AC: 23AN: 1459090Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 725566
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74338
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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 | Nov 01, 2022 | The c.1442C>T (p.P481L) alteration is located in exon 2 (coding exon 1) of the ZNF536 gene. This alteration results from a C to T substitution at nucleotide position 1442, causing the proline (P) at amino acid position 481 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
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T
Polyphen
0.15
.;B
Vest4
0.36
MutPred
Loss of disorder (P = 0.0658);Loss of disorder (P = 0.0658);
MVP
MPC
0.83
ClinPred
T
GERP RS
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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