X-70063203-C-A

Position:

• chrX-70063203-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207320.3(OTUD6A):​c.679C>A​(p.His227Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: OTUD6A NM_207320.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55

Genes affected

OTUD6A (HGNC:32312): (OTU deubiquitinase 6A) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA2 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD6A	NM_207320.3	c.679C>A	p.His227Asn	missense_variant	1/1	ENST00000338352.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD6A	ENST00000338352.3	c.679C>A	p.His227Asn	missense_variant	1/1		NM_207320.3	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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

Jan 26, 2022

The c.679C>A (p.H227N) alteration is located in exon 1 (coding exon 1) of the OTUD6A gene. This alteration results from a C to A substitution at nucleotide position 679, causing the histidine (H) at amino acid position 227 to be replaced by an asparagine (N). 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	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.038	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.16
Sift	Benign	0.054	T
Sift4G	Benign	0.11	T
Polyphen		0.79	P
Vest4		0.39
MutPred		0.47		Loss of catalytic residue at L229 (P = 0.0865);
MVP		0.35
MPC		1.6
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.40
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chrX-69283053;