rs150780889

Variant names:

• chr5-60599205-C-A
• rs150780889
• NM_018369.3:c.1298G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-60599205-C-A
• chr5-60599205-C-T

Variant summary

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

The NM_018369.3(DEPDC1B):​c.1298G>T​(p.Arg433Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R433H) 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: 1.78
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2820331).

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.1298G>T	p.Arg433Leu	missense	Exon 10 of 11	NP_060839.2	Q8WUY9-1
	DEPDC1B	NM_001145208.2		c.1243-1291G>T		intron	N/A	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.1298G>T	p.Arg433Leu	missense	Exon 10 of 11	ENSP00000265036.5	Q8WUY9-1
	DEPDC1B	ENST00000871249.1		c.1295G>T	p.Arg432Leu	missense	Exon 10 of 11	ENSP00000541308.1
	DEPDC1B	ENST00000927127.1		c.1298G>T	p.Arg433Leu	missense	Exon 10 of 11	ENSP00000597186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459646 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725978

African (AFR) AF: 0.00 AC: 0 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111260

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.8
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.074
Sift	Uncertain	0.017	D
Sift4G	Benign	0.072	T
Polyphen		0.13	B
Vest4		0.52
MutPred		0.46		Loss of disorder (P = 0.0502)
MVP		0.45
MPC		0.27
ClinPred		0.92	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.45
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs150780889; hg19: chr5-59895032;