rs5998144

Positions:

• chr22-31852258-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.3156-5187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 152,202 control chromosomes in the GnomAD database, including 577 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 0.081 (577 hom., cov: 32)
• Consequence: DEPDC5 NM_001242896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPDC5	NM_001242896.3	c.3156-5187T>C		intron_variant		ENST00000651528.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPDC5	ENST00000651528.2	c.3156-5187T>C		intron_variant			NM_001242896.3	P4

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 12353 AN: 152084 Hom.: 571 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0766

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

GnomAD4 genome AF: 0.0814 AC: 12382 AN: 152202 Hom.: 577 Cov.: 32 AF XY: 0.0803 AC XY: 5976 AN XY: 74422

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.0762

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0801 Hom.: 124

Bravo AF: 0.0869

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.59

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: rs5998144; hg19: chr22-32248244;