10-73792415-A-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_001367799.1(ZSWIM8):c.1876A>G(p.Ser626Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000455 in 1,604,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )
Consequence
ZSWIM8
NM_001367799.1 missense
NM_001367799.1 missense
Scores
3
12
Clinical Significance
Conservation
PhyloP100: 4.55
Genes affected
ZSWIM8 (HGNC:23528): (zinc finger SWIM-type containing 8) Enables ubiquitin ligase-substrate adaptor activity. Involved in positive regulation of miRNA catabolic process; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein ubiquitination. Part of Cul3-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ZSWIM8
BP4
?
Computational evidence support a benign effect (MetaRNN=0.07312679).
BS2
?
High AC in GnomAd at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZSWIM8 | NM_001367799.1 | c.1876A>G | p.Ser626Gly | missense_variant | 10/26 | ENST00000604729.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZSWIM8 | ENST00000604729.6 | c.1876A>G | p.Ser626Gly | missense_variant | 10/26 | 5 | NM_001367799.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152224Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000352 AC: 8AN: 227262Hom.: 0 AF XY: 0.0000404 AC XY: 5AN XY: 123634
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GnomAD4 exome AF: 0.0000427 AC: 62AN: 1452190Hom.: 0 Cov.: 32 AF XY: 0.0000457 AC XY: 33AN XY: 721636
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GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74376
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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 | Feb 06, 2024 | The c.1876A>G (p.S626G) alteration is located in exon 10 (coding exon 10) of the ZSWIM8 gene. This alteration results from a A to G substitution at nucleotide position 1876, causing the serine (S) at amino acid position 626 to be replaced by a glycine (G). 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
Benign
T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T
Polyphen
0.0
.;.;B;.;B
Vest4
MutPred
Loss of phosphorylation at S626 (P = 0.0132);Loss of phosphorylation at S626 (P = 0.0132);Loss of phosphorylation at S626 (P = 0.0132);Loss of phosphorylation at S626 (P = 0.0132);Loss of phosphorylation at S626 (P = 0.0132);
MVP
MPC
0.047
ClinPred
T
GERP RS
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