chr22-31768804-C-T

Variant names:

• chr22-31768804-C-T
• rs116263417
• NM_001242896.3:c.364-10C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001242896.3(DEPDC5):​c.364-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,611,876 control chromosomes in the GnomAD database, including 1,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (108 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1025 hom.)
• Consequence: DEPDC5 NM_001242896.3 intron
• Scores: Splicing: ADA: 0.00001226
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.689

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 22-31768804-C-T is Benign according to our data. Variant chr22-31768804-C-T is described in ClinVar as [Benign]. Clinvar id is 257662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-31768804-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.364-10C>T		intron_variant	Intron 6 of 42	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.364-10C>T		intron_variant	Intron 6 of 42		NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.280-10C>T		intron_variant	Intron 4 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5123 AN: 152082 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.0185

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0638

Gnomad FIN AF: 0.0828

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0345

GnomAD3 exomes AF: 0.0359 AC: 8910 AN: 248018 Hom.: 226 AF XY: 0.0379 AC XY: 5104 AN XY: 134572

Gnomad AFR exome AF: 0.0270

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0237

Gnomad EAS exome AF: 0.0200

Gnomad SAS exome AF: 0.0541

Gnomad FIN exome AF: 0.0771

Gnomad NFE exome AF: 0.0343

Gnomad OTH exome AF: 0.0321

GnomAD4 exome AF: 0.0346 AC: 50460 AN: 1459676 Hom.: 1025 Cov.: 32 AF XY: 0.0353 AC XY: 25632 AN XY: 726204

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.0166

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0264

Gnomad4 SAS exome AF: 0.0564

Gnomad4 FIN exome AF: 0.0726

Gnomad4 NFE exome AF: 0.0326

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0337 AC: 5122 AN: 152200 Hom.: 108 Cov.: 32 AF XY: 0.0369 AC XY: 2743 AN XY: 74422

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0185

Gnomad4 EAS AF: 0.0222

Gnomad4 SAS AF: 0.0638

Gnomad4 FIN AF: 0.0828

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0337

Alfa AF: 0.0266 Hom.: 21

Bravo AF: 0.0275

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial focal epilepsy with variable foci Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.26

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0060
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: rs116263417; hg19: chr22-32164790; COSMIC: COSV56700724;