rs1555933874

Variant names:

• chr22-31897540-A-C
• rs1555933874
• NM_001242896.3:c.4262A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-31897540-A-C
• chr22-31897540-A-G

Variant summary

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

The NM_001242896.3(DEPDC5):​c.4262A>C​(p.Glu1421Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC5 NM_001242896.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC5	NM_001242896.3	c.4262A>C	p.Glu1421Ala	missense_variant	Exon 40 of 43	ENST00000651528.2	NP_001229825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC5	ENST00000651528.2	c.4262A>C	p.Glu1421Ala	missense_variant	Exon 40 of 43		NM_001242896.3	ENSP00000498382.1
ENSG00000285404	ENST00000646701.1	c.1787-58599A>C		intron_variant	Intron 20 of 20			ENSP00000496158.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 16, 2016

Athena Diagnostics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.011	.;.;.;.;.;T;.;.;.;.;T;.;.;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D;.;.;D;D;.;D;.;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;.;.;.;.;L;.;.;.;.;L;.;.;L;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	0.57	N;.;.;.;.;.;N;.;.;.;N;.;.;N;.
REVEL	Uncertain	0.31
Sift	Benign	1.0	T;.;.;.;.;.;T;.;.;.;T;.;.;T;.
Sift4G	Benign	0.75	T;.;.;.;.;.;T;.;.;.;T;.;.;T;.
Polyphen		1.0	.;.;D;.;.;.;.;.;.;.;.;.;D;.;.
Vest4		0.71
MVP		0.25
MPC		2.6
ClinPred		0.97	D
GERP RS		5.6
Varity_R		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: rs1555933874; hg19: chr22-32293526;