rs16989600

chr22-31879956-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242896.3(DEPDC5):c.4033+204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0659 in 579,228 control chromosomes in the GnomAD database, including 1,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (569 hom., cov: 32)
  • Exomes 𝑓: 0.061 (973 hom.)
• Consequence: DEPDC5 NM_001242896.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 22-31879956-C-T is Benign according to our data. Variant chr22-31879956-C-T is described in ClinVar as [Benign]. Clinvar id is 1269081.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.4033+204C>T		intron_variant		ENST00000651528.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPDC5	ENST00000651528.2	c.4033+204C>T		intron_variant			NM_001242896.3	P4

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12281 AN: 152040 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0405

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0755

GnomAD4 exome AF: 0.0606 AC: 25883 AN: 427070 Hom.: 973 Cov.: 4 AF XY: 0.0588 AC XY: 13230 AN XY: 224994

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0600

Gnomad4 EAS exome AF: 0.0205

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0814

Gnomad4 NFE exome AF: 0.0577

Gnomad4 OTH exome AF: 0.0647

GnomAD4 genome AF: 0.0809 AC: 12310 AN: 152158 Hom.: 569 Cov.: 32 AF XY: 0.0801 AC XY: 5961 AN XY: 74396

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0586

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0763

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0752

Alfa AF: 0.0843 Hom.: 123

Bravo AF: 0.0864

Asia WGS AF: 0.0600 AC: 207 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	9.6
Dann	Benign	0.90

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: rs16989600; hg19: chr22-32275942;