NM_018369.3:c.1217G>C

Variant names:

• chr5-60603416-C-G
• rs754576713
• NM_018369.3:c.1217G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018369.3(DEPDC1B):​c.1217G>C​(p.Arg406Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,438,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R406H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DEPDC1B NM_018369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

Genes affected

DEPDC1B (HGNC:24902): (DEP domain containing 1B) Predicted to enable GTPase activator activity. Involved in cell migration and positive regulation of Wnt signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018369.3. 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
	DEPDC1B	NM_018369.3	MANE Select	c.1217G>C	p.Arg406Pro	missense	Exon 9 of 11	NP_060839.2	Q8WUY9-1
	DEPDC1B	NM_001145208.2		c.1217G>C	p.Arg406Pro	missense	Exon 9 of 10	NP_001138680.1	Q8WUY9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC1B	ENST00000265036.10	TSL:1 MANE Select	c.1217G>C	p.Arg406Pro	missense	Exon 9 of 11	ENSP00000265036.5	Q8WUY9-1
	DEPDC1B	ENST00000871249.1		c.1214G>C	p.Arg405Pro	missense	Exon 9 of 11	ENSP00000541308.1
	DEPDC1B	ENST00000927127.1		c.1217G>C	p.Arg406Pro	missense	Exon 9 of 11	ENSP00000597186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438868 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 715540

African (AFR) AF: 0.00 AC: 0 AN: 32070

American (AMR) AF: 0.00 AC: 0 AN: 38184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39038

South Asian (SAS) AF: 0.00 AC: 0 AN: 81668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105040

Other (OTH) AF: 0.00 AC: 0 AN: 59278

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.089	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.4
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.45
Sift	Benign	0.031	D
Sift4G	Uncertain	0.021	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.42		Loss of catalytic residue at R406 (P = 0.053)
MVP		0.92
MPC		0.46
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.67
gMVP		0.76
Mutation Taster		=55/45	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

dbSNP: rs754576713; hg19: chr5-59899243;