15-31483422-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001382637.1(OTUD7A):c.2674C>T(p.Pro892Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000584 in 1,370,812 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 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
OTUD7A
NM_001382637.1 missense
NM_001382637.1 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 5.30
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.08526152).
BS2
High AC in GnomAdExome4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTUD7A | NM_001382637.1 | c.2674C>T | p.Pro892Ser | missense_variant | 13/13 | ENST00000307050.6 | NP_001369566.1 | |
OTUD7A | NM_130901.3 | c.2653C>T | p.Pro885Ser | missense_variant | 14/14 | NP_570971.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTUD7A | ENST00000307050.6 | c.2674C>T | p.Pro892Ser | missense_variant | 13/13 | 1 | NM_001382637.1 | ENSP00000305926.5 | ||
OTUD7A | ENST00000560598.2 | c.2653C>T | p.Pro885Ser | missense_variant | 14/14 | 5 | ENSP00000453883.2 | |||
OTUD7A | ENST00000678495.1 | c.2653C>T | p.Pro885Ser | missense_variant | 11/11 | ENSP00000503326.1 |
Frequencies
GnomAD3 genomes AF: 0.00000669 AC: 1AN: 149370Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
149370
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000668 AC: 3AN: 44878Hom.: 0 AF XY: 0.000110 AC XY: 3AN XY: 27268
GnomAD3 exomes
AF:
AC:
3
AN:
44878
Hom.:
AF XY:
AC XY:
3
AN XY:
27268
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000573 AC: 7AN: 1221442Hom.: 0 Cov.: 28 AF XY: 0.00000832 AC XY: 5AN XY: 601128
GnomAD4 exome
AF:
AC:
7
AN:
1221442
Hom.:
Cov.:
28
AF XY:
AC XY:
5
AN XY:
601128
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000669 AC: 1AN: 149370Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 72808
GnomAD4 genome
AF:
AC:
1
AN:
149370
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
72808
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ExAC
AF:
AC:
2
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 | Jun 05, 2023 | The c.2653C>T (p.P885S) 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 2653, causing the proline (P) at amino acid position 885 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
Benign
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of MoRF binding (P = 0.0286);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at