1-149944297-T-G

Variant names:

• chr1-149944297-T-G
• rs781876541
• NM_020205.4:c.2092A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020205.4(OTUD7B):​c.2092A>C​(p.Ile698Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I698V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD7B NM_020205.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

Genes affected

OTUD7B (HGNC:16683): (OTU deubiquitinase 7B) Enables Lys48-specific deubiquitinase activity and thiol-dependent deubiquitinase. Involved in several processes, including negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of macromolecule metabolic process; and protein deubiquitination. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09374872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020205.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7B	NM_020205.4	MANE Select	c.2092A>C	p.Ile698Leu	missense	Exon 12 of 12	NP_064590.2	Q6GQQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7B	ENST00000581312.6	TSL:1 MANE Select	c.2092A>C	p.Ile698Leu	missense	Exon 12 of 12	ENSP00000462729.1	Q6GQQ9-1
	OTUD7B	ENST00000907908.1		c.2119A>C	p.Ile707Leu	missense	Exon 12 of 12	ENSP00000577967.1
	OTUD7B	ENST00000907909.1		c.2092A>C	p.Ile698Leu	missense	Exon 12 of 12	ENSP00000577968.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.6
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.72	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.33		Gain of catalytic residue at I698 (P = 0.0019)
MVP		0.29
ClinPred		0.16	T
GERP RS		2.1
Varity_R		0.070
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs781876541; hg19: chr1-149916196;