15-31483788-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16765743).
• BS2: High AC in GnomAd at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.2308C>T	p.Pro770Ser	missense_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3	c.2287C>T	p.Pro763Ser	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2308C>T	p.Pro770Ser	missense_variant	13/13	1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.2287C>T	p.Pro763Ser	missense_variant	14/14	5		A2
OTUD7A	ENST00000678495.1	c.2287C>T	p.Pro763Ser	missense_variant	11/11			A2

Frequencies

GnomAD3 genomes AF: 0.000659 AC: 96 AN: 145772 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00156

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000991

Gnomad OTH AF: 0.00100

GnomAD4 exome AF: 0.000561 AC: 504 AN: 897992 Hom.: 0 Cov.: 28 AF XY: 0.000553 AC XY: 232 AN XY: 419582

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.000952

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000541

Gnomad4 NFE exome AF: 0.000601

Gnomad4 OTH exome AF: 0.000382

GnomAD4 genome AF: 0.000658 AC: 96 AN: 145882 Hom.: 0 Cov.: 31 AF XY: 0.000592 AC XY: 42 AN XY: 70996

Gnomad4 AFR AF: 0.000123

Gnomad4 AMR AF: 0.00156

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000991

Gnomad4 OTH AF: 0.000988

Alfa AF: 0.00165 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.58	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.20
Sift	Uncertain	0.015	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.14
MVP		0.18
ClinPred		0.97	D
GERP RS		3.6
Varity_R		0.12
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs564071366; hg19: chr15-31775991;