chr15-31537504-C-G

Variant names:

• chr15-31537504-C-G
• rs2125623
• NM_001382637.1:c.551-6696G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382637.1(OTUD7A):​c.551-6696G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544
• Publications: 13 publications found

Genes affected

OTUD7A (HGNC:20718): (OTU deubiquitinase 7A) The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

OTUD7A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.551-6696G>C		intron_variant	Intron 5 of 12	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.551-6696G>C		intron_variant	Intron 6 of 13		NP_570971.1
OTUD7A	NM_001329907.2	c.551-6696G>C		intron_variant	Intron 6 of 10		NP_001316836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.551-6696G>C		intron_variant	Intron 5 of 12	1	NM_001382637.1	ENSP00000305926.5
OTUD7A	ENST00000560598.2	c.551-6696G>C		intron_variant	Intron 6 of 13	5		ENSP00000453883.2
OTUD7A	ENST00000678495.1	c.551-6696G>C		intron_variant	Intron 3 of 10			ENSP00000503326.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 29425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.056
DANN	Benign	0.40
PhyloP100		-0.54

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: rs2125623; hg19: chr15-31829707;