chr10-23439542-G-T

Position:

• chr10-23439542-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145373.3(OTUD1):​c.85G>T​(p.Ala29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000163 in 1,229,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: OTUD1 NM_001145373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.865

Genes affected

OTUD1 (HGNC:27346): (OTU deubiquitinase 1) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA7 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

ENSG00000287124 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.124694884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD1	NM_001145373.3	c.85G>T	p.Ala29Ser	missense_variant	1/1	ENST00000376495.5	NP_001138845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD1	ENST00000376495.5	c.85G>T	p.Ala29Ser	missense_variant	1/1	6	NM_001145373.3	ENSP00000365678.3
ENSG00000287124	ENST00000702412.1	n.88+497G>T		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000163 AC: 2 AN: 1229272 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 604962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 16, 2022

The c.85G>T (p.A29S) alteration is located in exon 1 (coding exon 1) of the OTUD1 gene. This alteration results from a G to T substitution at nucleotide position 85, causing the alanine (A) at amino acid position 29 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	0.090
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.3
DANN	Benign	0.68
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.39	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.047
Sift	Benign	0.20	T
Sift4G	Benign	0.52	T
Polyphen		0.66	P
Vest4		0.070
MutPred		0.18		Gain of glycosylation at A29 (P = 2e-04);
MVP		0.15
ClinPred		0.16	T
GERP RS		0.14
Varity_R		0.093
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-23728471;