12-100262365-C-A

Variant names:

• chr12-100262365-C-A
• rs781643612
• NM_001364818.2:c.599G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364818.2(DEPDC4):​c.599G>T​(p.Gly200Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DEPDC4 NM_001364818.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.01
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07747537).

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.599G>T	p.Gly200Val	missense	Exon 3 of 10	NP_001351747.1	E9PGM3
	DEPDC4	NM_001387201.1		c.599G>T	p.Gly200Val	missense	Exon 3 of 11	NP_001374130.1
	DEPDC4	NM_001387205.1		c.599G>T	p.Gly200Val	missense	Exon 3 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.599G>T	p.Gly200Val	missense	Exon 3 of 10	ENSP00000448385.2	E9PGM3
	DEPDC4	ENST00000549249.5	TSL:1	c.398G>T	p.Gly133Val	missense	Exon 3 of 7	ENSP00000448338.1	Q3ZCN8
	DEPDC4	ENST00000416321.5	TSL:1	c.599G>T	p.Gly200Val	missense	Exon 3 of 5	ENSP00000396234.1	Q8N2C3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460960 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726804

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 33

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	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.0
DANN	Benign	0.81
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.024
Sift	Benign	0.26	T
Sift4G	Benign	0.29	T
Polyphen		0.063	B
Vest4		0.13
MutPred		0.44		Loss of disorder (P = 0.0358)
MVP		0.29
MPC		0.050
ClinPred		0.30	T
GERP RS		-3.4
PromoterAI		-0.0038	Neutral
Varity_R		0.082
gMVP		0.14
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs781643612; hg19: chr12-100656143;