1-149943965-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020205.4(OTUD7B):​c.2424C>A​(p.Ser808Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OTUD7B
NM_020205.4 missense

Scores

1
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
Variant links:
Genes affected
OTUD7B (HGNC:16683): (OTU deubiquitinase 7B) Enables Lys48-specific deubiquitinase activity and thiol-dependent deubiquitinase. Involved in several processes, including negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of macromolecule metabolic process; and protein deubiquitination. Located in cytoplasm and 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3203761).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OTUD7BNM_020205.4 linkuse as main transcriptc.2424C>A p.Ser808Arg missense_variant 12/12 ENST00000581312.6 NP_064590.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OTUD7BENST00000581312.6 linkuse as main transcriptc.2424C>A p.Ser808Arg missense_variant 12/121 NM_020205.4 ENSP00000462729 P1Q6GQQ9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 31, 2024The c.2424C>A (p.S808R) alteration is located in exon 12 (coding exon 11) of the OTUD7B gene. This alteration results from a C to A substitution at nucleotide position 2424, causing the serine (S) at amino acid position 808 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.048
T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
0.99
D
PrimateAI
Pathogenic
0.81
D
Sift4G
Uncertain
0.017
D
Polyphen
0.85
P
Vest4
0.45
MutPred
0.42
Gain of catalytic residue at S808 (P = 0.0107);
MVP
0.49
ClinPred
0.73
D
GERP RS
4.6
Varity_R
0.17
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-149915864; API