12-100256190-T-C

Variant names:

• chr12-100256190-T-C
• NM_001364818.2:c.737A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001364818.2(DEPDC4):​c.737A>G​(p.Gln246Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Q246Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC4 NM_001364818.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

Genes affected

DEPDC4 (HGNC:22952): (DEP domain containing 4) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41918746).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364818.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC4	NM_001364818.2	MANE Select	c.737A>G	p.Gln246Arg	missense	Exon 4 of 10	NP_001351747.1	E9PGM3
	DEPDC4	NM_001387201.1		c.776A>G	p.Gln259Arg	missense	Exon 5 of 11	NP_001374130.1
	DEPDC4	NM_001387205.1		c.737A>G	p.Gln246Arg	missense	Exon 4 of 9	NP_001374134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC4	ENST00000550587.6	TSL:1 MANE Select	c.737A>G	p.Gln246Arg	missense	Exon 4 of 10	ENSP00000448385.2	E9PGM3
	DEPDC4	ENST00000549249.5	TSL:1	c.575A>G	p.Gln192Arg	missense	Exon 5 of 7	ENSP00000448338.1	Q3ZCN8
	DEPDC4	ENST00000416321.5	TSL:1	c.737A>G	p.Gln246Arg	missense	Exon 4 of 5	ENSP00000396234.1	Q8N2C3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.68
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.50
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.6
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.22
Sift	Benign	0.061	T
Sift4G	Benign	0.099	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.69		Gain of sheet (P = 0.0827)
MVP		0.45
MPC		0.20
ClinPred		0.81	D
GERP RS		3.9
Varity_R		0.15
gMVP		0.23
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr12-100649968; COSMIC: COSV54553800; COSMIC: COSV54553800;