5-60605697-C-T

Variant names:

• chr5-60605697-C-T
• NM_018369.3:c.1058G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018369.3(DEPDC1B):​c.1058G>A​(p.Arg353Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DEPDC1B NM_018369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3	c.1058G>A	p.Arg353Gln	missense_variant	Exon 8 of 11	ENST00000265036.10	NP_060839.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC1B	ENST00000265036.10	c.1058G>A	p.Arg353Gln	missense_variant	Exon 8 of 11	1	NM_018369.3	ENSP00000265036.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458278 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 18, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1058G>A (p.R353Q) alteration is located in exon 8 (coding exon 8) of the DEPDC1B gene. This alteration results from a G to A substitution at nucleotide position 1058, causing the arginine (R) at amino acid position 353 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.49	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.99	D;.
Vest4		0.86
MutPred		0.66		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.73
MPC		0.52
ClinPred		1.0	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-59901524; COSMIC: COSV54008880;