rs201775933

Variant names:

• chr1-149943927-C-A
• rs201775933
• NM_020205.4:c.2462G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-149943927-C-A
• chr1-149943927-C-G
• chr1-149943927-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020205.4(OTUD7B):​c.2462G>T​(p.Cys821Phe) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C821Y) 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: 0.817

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30738074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7B	NM_020205.4	c.2462G>T	p.Cys821Phe	missense_variant	Exon 12 of 12	ENST00000581312.6	NP_064590.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7B	ENST00000581312.6	c.2462G>T	p.Cys821Phe	missense_variant	Exon 12 of 12	1	NM_020205.4	ENSP00000462729.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.67
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.087
Eigen_PC	Benign	0.00051
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.76	T
Sift4G	Benign	0.49	T
Polyphen		0.58	P
Vest4		0.41
MutPred		0.67		Loss of disorder (P = 0.1101);
MVP		0.32
ClinPred		0.43	T
GERP RS		3.6
Varity_R		0.39
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201775933; hg19: chr1-149915826;