rs771270766

Variant names:

• chr22-31792041-C-A
• NM_001242896.3:c.633C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-31792041-C-A
• chr22-31792041-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242896.3(DEPDC5):​c.633C>A​(p.Asn211Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,470 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DEPDC5 NM_001242896.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25307077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.633C>A	p.Asn211Lys	missense_variant	Exon 11 of 43	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.633C>A	p.Asn211Lys	missense_variant	Exon 11 of 43		NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.549C>A	p.Asn183Lys	missense_variant	Exon 9 of 21			ENSP00000496158.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453470 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723152

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D;D;D;D;D;.;.;D;D;.;.;D;D;.;D;D;D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.62	N;.;.;N;N;.;.;N;N;.;N;.;N;.;N;N;.;.;N;N;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D;.;.;.;.;.;.;.;D;.;D;.;.;.;D;D;.;.;D;D;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.010	D;.;.;.;.;.;.;.;T;.;D;.;.;.;T;T;.;.;D;T;.;.
Sift4G	Benign	0.19	T;.;.;.;.;.;.;.;D;.;D;.;.;.;T;D;.;.;D;T;.;.
Polyphen		0.18, 1.0	.;.;.;.;.;.;.;B;D;.;.;.;.;.;B;D;.;.;.;.;.;.
Vest4		0.55
MutPred		0.43		Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);Gain of methylation at N211 (P = 0.0022);.;
MVP		0.27
MPC		1.3
ClinPred		0.98	D
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-32188027;