chr22-41604053-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015704.3(DESI1):c.281C>T(p.Ser94Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,612,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
DESI1
NM_015704.3 missense
NM_015704.3 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 5.39
Genes affected
DESI1 (HGNC:24577): (desumoylating isopeptidase 1) Enables importin-alpha family protein binding activity. Involved in protein export from nucleus and regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DESI1 | NM_015704.3 | c.281C>T | p.Ser94Phe | missense_variant | 4/6 | ENST00000263256.7 | NP_056519.1 | |
DESI1 | XM_047441335.1 | c.209C>T | p.Ser70Phe | missense_variant | 5/7 | XP_047297291.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DESI1 | ENST00000263256.7 | c.281C>T | p.Ser94Phe | missense_variant | 4/6 | 1 | NM_015704.3 | ENSP00000263256 | P1 | |
DESI1 | ENST00000463886.1 | n.173C>T | non_coding_transcript_exon_variant | 1/3 | 2 | |||||
DESI1 | ENST00000482612.1 | n.35C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151998Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249964Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135348
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460854Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726740
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
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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 | Sep 20, 2023 | The c.281C>T (p.S94F) alteration is located in exon 4 (coding exon 4) of the DESI1 gene. This alteration results from a C to T substitution at nucleotide position 281, causing the serine (S) at amino acid position 94 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of disorder (P = 0.0049);
MVP
MPC
ClinPred
D
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