chr10-23439524-C-T

Position:

• chr10-23439524-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145373.3(OTUD1):​c.67C>T​(p.Pro23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000823 in 1,215,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: OTUD1 NM_001145373.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.607

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029208481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD1	NM_001145373.3	c.67C>T	p.Pro23Ser	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.67C>T	p.Pro23Ser	missense_variant	1/1	6	NM_001145373.3	ENSP00000365678.3
ENSG00000287124	ENST00000702412.1	n.88+479C>T		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.23e-7 AC: 1 AN: 1215090 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 596494

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: 0.00

Gnomad4 OTH exome AF: 0.0000204

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 29, 2024

The c.67C>T (p.P23S) alteration is located in exon 1 (coding exon 1) of the OTUD1 gene. This alteration results from a C to T substitution at nucleotide position 67, causing the proline (P) at amino acid position 23 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	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.39	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.54	N
REVEL	Benign	0.022
Sift	Benign	0.94	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.077
MutPred		0.19		Gain of phosphorylation at P23 (P = 0.0331);
MVP		0.061
ClinPred		0.089	T
GERP RS		-3.2
Varity_R		0.029
gMVP		0.28

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: rs1847102083; hg19: chr10-23728453;