chr15-31483779-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001382637.1(OTUD7A):c.2317C>T(p.Pro773Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000711 in 1,054,430 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 0.000062 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
OTUD7A
NM_001382637.1 missense
NM_001382637.1 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 7.62
Genes affected
OTUD7A (HGNC:20718): (OTU deubiquitinase 7A) The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]
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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=0.08650109).
BS2
?
High AC in GnomAd at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTUD7A | NM_001382637.1 | c.2317C>T | p.Pro773Ser | missense_variant | 13/13 | ENST00000307050.6 | |
OTUD7A | NM_130901.3 | c.2296C>T | p.Pro766Ser | missense_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTUD7A | ENST00000307050.6 | c.2317C>T | p.Pro773Ser | missense_variant | 13/13 | 1 | NM_001382637.1 | P2 | |
OTUD7A | ENST00000560598.2 | c.2296C>T | p.Pro766Ser | missense_variant | 14/14 | 5 | A2 | ||
OTUD7A | ENST00000678495.1 | c.2296C>T | p.Pro766Ser | missense_variant | 11/11 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000616 AC: 9AN: 146052Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000727 AC: 66AN: 908276Hom.: 0 Cov.: 28 AF XY: 0.0000777 AC XY: 33AN XY: 424818
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GnomAD4 genome ? AF: 0.0000616 AC: 9AN: 146154Hom.: 0 Cov.: 32 AF XY: 0.000112 AC XY: 8AN XY: 71112
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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 11, 2022 | The c.2296C>T (p.P766S) alteration is located in exon 11 (coding exon 11) of the OTUD7A gene. This alteration results from a C to T substitution at nucleotide position 2296, causing the proline (P) at amino acid position 766 to be replaced by a serine (S). 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0024);
MVP
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