rs1447581156

Variant names:

• chr5-60638884-T-A
• rs1447581156
• NM_018369.3:c.764A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-60638884-T-A
• chr5-60638884-T-C

Variant summary

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

The NM_018369.3(DEPDC1B):​c.764A>T​(p.Asn255Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. 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. N255S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DEPDC1B NM_018369.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• 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=0.27969435).

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.764A>T	p.Asn255Ile	missense	Exon 7 of 11	NP_060839.2	Q8WUY9-1
	DEPDC1B	NM_001145208.2		c.764A>T	p.Asn255Ile	missense	Exon 7 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.764A>T	p.Asn255Ile	missense	Exon 7 of 11	ENSP00000265036.5	Q8WUY9-1
	DEPDC1B	ENST00000871249.1		c.761A>T	p.Asn254Ile	missense	Exon 7 of 11	ENSP00000541308.1
	DEPDC1B	ENST00000927127.1		c.764A>T	p.Asn255Ile	missense	Exon 7 of 11	ENSP00000597186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.11
Sift	Benign	0.068	T
Sift4G	Benign	0.079	T
Polyphen		0.0010	B
Vest4		0.43
MutPred		0.65		Loss of helix (P = 0.0376)
MVP		0.53
MPC		0.21
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.23
gMVP		0.38
Mutation Taster		=85/15	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: rs1447581156; hg19: chr5-59934711;