5-60603431-G-T

Variant names:

• chr5-60603431-G-T
• rs1035026050
• NM_018369.3:c.1202C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018369.3(DEPDC1B):​c.1202C>A​(p.Thr401Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,459,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DEPDC1B NM_018369.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.86

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093535334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1B	NM_018369.3	c.1202C>A	p.Thr401Asn	missense_variant	Exon 9 of 11	ENST00000265036.10	NP_060839.2
DEPDC1B	NM_001145208.2	c.1202C>A	p.Thr401Asn	missense_variant	Exon 9 of 10		NP_001138680.1
DEPDC1B	XM_011543509.3	c.1157C>A	p.Thr386Asn	missense_variant	Exon 9 of 11		XP_011541811.1
DEPDC1B	XM_047417369.1	c.1157C>A	p.Thr386Asn	missense_variant	Exon 9 of 10		XP_047273325.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC1B	ENST00000265036.10	c.1202C>A	p.Thr401Asn	missense_variant	Exon 9 of 11	1	NM_018369.3	ENSP00000265036.5
DEPDC1B	ENST00000453022.6	c.1202C>A	p.Thr401Asn	missense_variant	Exon 9 of 10	2		ENSP00000389101.2
DEPDC1B	ENST00000512078.5	n.*1199C>A		non_coding_transcript_exon_variant	Exon 10 of 11	2		ENSP00000427527.1
DEPDC1B	ENST00000512078.5	n.*1199C>A		3_prime_UTR_variant	Exon 10 of 11	2		ENSP00000427527.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1459006 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 725834

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1202C>A (p.T401N) alteration is located in exon 9 (coding exon 9) of the DEPDC1B gene. This alteration results from a C to A substitution at nucleotide position 1202, causing the threonine (T) at amino acid position 401 to be replaced by an asparagine (N). 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	0.060
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.033	T;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.044
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.72	N;N
REVEL	Benign	0.046
Sift	Benign	0.43	T;T
Sift4G	Benign	0.53	T;T
Polyphen		0.0	B;.
Vest4		0.24
MVP		0.45
MPC		0.19
ClinPred		0.30	T
GERP RS		4.1
Varity_R		0.12
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1035026050; hg19: chr5-59899258;