15-31501727-A-G

Variant names:

• chr15-31501727-A-G
• rs7164569
• NM_001382637.1:c.1134T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001382637.1(OTUD7A):​c.1134T>C​(p.Leu378Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,613,672 control chromosomes in the GnomAD database, including 103,573 homozygotes. 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: 𝑓 0.37 (10935 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92638 hom.)
• Consequence: OTUD7A NM_001382637.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 19 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.1134T>C	p.Leu378Leu	synonymous_variant	Exon 10 of 13	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.1113T>C	p.Leu371Leu	synonymous_variant	Exon 11 of 14		NP_570971.1
OTUD7A	NM_001329907.2	c.1134T>C	p.Leu378Leu	synonymous_variant	Exon 11 of 11		NP_001316836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.1134T>C	p.Leu378Leu	synonymous_variant	Exon 10 of 13	1	NM_001382637.1	ENSP00000305926.5
OTUD7A	ENST00000560598.2	c.1113T>C	p.Leu371Leu	synonymous_variant	Exon 11 of 14	5		ENSP00000453883.2
OTUD7A	ENST00000678495.1	c.1113T>C	p.Leu371Leu	synonymous_variant	Exon 8 of 11			ENSP00000503326.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56369 AN: 151896 Hom.: 10916 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.351

GnomAD2 exomes AF: 0.336 AC: 84501 AN: 251424 AF XY: 0.327

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.408

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.251

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.352 AC: 514560 AN: 1461658 Hom.: 92638 Cov.: 52 AF XY: 0.347 AC XY: 252307 AN XY: 727126

African (AFR) AF: 0.477 AC: 15959 AN: 33478

American (AMR) AF: 0.396 AC: 17686 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 8281 AN: 26130

East Asian (EAS) AF: 0.248 AC: 9863 AN: 39696

South Asian (SAS) AF: 0.214 AC: 18487 AN: 86252

European-Finnish (FIN) AF: 0.280 AC: 14962 AN: 53416

Middle Eastern (MID) AF: 0.251 AC: 1446 AN: 5766

European-Non Finnish (NFE) AF: 0.366 AC: 407054 AN: 1111822

Other (OTH) AF: 0.345 AC: 20822 AN: 60380

GnomAD4 genome AF: 0.371 AC: 56431 AN: 152014 Hom.: 10935 Cov.: 32 AF XY: 0.363 AC XY: 26954 AN XY: 74302

African (AFR) AF: 0.477 AC: 19777 AN: 41456

American (AMR) AF: 0.342 AC: 5215 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3472

East Asian (EAS) AF: 0.252 AC: 1303 AN: 5166

South Asian (SAS) AF: 0.212 AC: 1025 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2804 AN: 10560

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24119 AN: 67948

Other (OTH) AF: 0.352 AC: 744 AN: 2114

Alfa AF: 0.367 Hom.: 23383

Bravo AF: 0.388

Asia WGS AF: 0.271 AC: 945 AN: 3478

EpiCase AF: 0.348

EpiControl AF: 0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.56
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs7164569; hg19: chr15-31793930; COSMIC: COSV108134088;