15-31483788-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001382637.1(OTUD7A):c.2308C>T(p.Pro770Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000575 in 1,043,874 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 0.00066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00056 ( 0 hom. )
Consequence
OTUD7A
NM_001382637.1 missense
NM_001382637.1 missense
Scores
2
3
14
Clinical Significance
Conservation
PhyloP100: 7.66
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=0.16765743).
BS2
High AC in GnomAd4 at 96 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTUD7A | ENST00000307050.6 | c.2308C>T | p.Pro770Ser | missense_variant | 13/13 | 1 | NM_001382637.1 | ENSP00000305926.5 | ||
OTUD7A | ENST00000560598.2 | c.2287C>T | p.Pro763Ser | missense_variant | 14/14 | 5 | ENSP00000453883.2 | |||
OTUD7A | ENST00000678495.1 | c.2287C>T | p.Pro763Ser | missense_variant | 11/11 | ENSP00000503326.1 |
Frequencies
GnomAD3 genomes AF: 0.000659 AC: 96AN: 145772Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.000561 AC: 504AN: 897992Hom.: 0 Cov.: 28 AF XY: 0.000553 AC XY: 232AN XY: 419582
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GnomAD4 genome AF: 0.000658 AC: 96AN: 145882Hom.: 0 Cov.: 31 AF XY: 0.000592 AC XY: 42AN XY: 70996
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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 | Aug 12, 2021 | The c.2287C>T (p.P763S) 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 2287, causing the proline (P) at amino acid position 763 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MVP
ClinPred
D
GERP RS
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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