rs5998126

Positions:

• chr22-31782416-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242896.3(DEPDC5):​c.484-1491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,060 control chromosomes in the GnomAD database, including 9,434 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 0.33 (9434 hom., cov: 32)
• Consequence: DEPDC5 NM_001242896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

Genes affected

DEPDC5 (HGNC:18423): (DEP domain containing 5, GATOR1 subcomplex subunit) This gene encodes a member of the IML1 family of proteins involved in G-protein signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth by sensing the availability of nutrients. The protein encoded by this gene is a component of the GATOR1 (GAP activity toward Rags) complex which inhibits the amino acid-sensing branch of the mTORC1 pathway. Mutations in this gene are associated with autosomal dominant familial focal epilepsy with variable foci. A single nucleotide polymorphism in an intron of this gene has been associated with an increased risk of hepatocellular carcinoma in individuals with chronic hepatitis C virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ENSG00000285404 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.484-1491T>C		intron_variant		ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.484-1491T>C		intron_variant			NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.400-1491T>C		intron_variant				ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49955 AN: 151942 Hom.: 9396 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.329 AC: 50042 AN: 152060 Hom.: 9434 Cov.: 32 AF XY: 0.329 AC XY: 24474 AN XY: 74306

Gnomad4 AFR AF: 0.527

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.299

Alfa AF: 0.298 Hom.: 911

Bravo AF: 0.338

Asia WGS AF: 0.317 AC: 1105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.47

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: rs5998126; hg19: chr22-32178402;