1-68496956-T-C

Variant names:

• chr1-68496956-T-C
• rs1646270344
• NM_001114120.3:c.44A>G

Variant summary

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

The NM_001114120.3(DEPDC1):​c.44A>G​(p.Lys15Arg) 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. 13/21 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)
• Consequence: DEPDC1 NM_001114120.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.431

Genes affected

DEPDC1 (HGNC:22949): (DEP domain containing 1) Predicted to enable GTPase activator activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleus. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

DEPDC1-AS1 (HGNC:50592): (DEPDC1 antisense RNA 1)

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=0.19361618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DEPDC1	NM_001114120.3	c.44A>G	p.Lys15Arg	missense_variant	Exon 1 of 12	ENST00000456315.7	NP_001107592.1
DEPDC1	NM_017779.6	c.44A>G	p.Lys15Arg	missense_variant	Exon 1 of 11		NP_060249.2
DEPDC1-AS1	NR_110671.1	n.96+185T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DEPDC1	ENST00000456315.7	c.44A>G	p.Lys15Arg	missense_variant	Exon 1 of 12	1	NM_001114120.3	ENSP00000412292.2
DEPDC1	ENST00000370966.9	c.44A>G	p.Lys15Arg	missense_variant	Exon 1 of 11	1		ENSP00000360005.5
DEPDC1-AS1	ENST00000428732.1	n.96+185T>C		intron_variant	Intron 1 of 2	1
DEPDC1	ENST00000525124.1	c.-354A>G		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000431477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44A>G (p.K15R) alteration is located in exon 1 (coding exon 1) of the DEPDC1 gene. This alteration results from a A to G substitution at nucleotide position 44, causing the lysine (K) at amino acid position 15 to be replaced by an arginine (R). 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	0.068
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.16	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.022
Sift	Benign	0.20	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.090	B;B
Vest4		0.18
MutPred		0.32		Loss of methylation at K15 (P = 0.0099);Loss of methylation at K15 (P = 0.0099);
MVP		0.27
MPC		0.10
ClinPred		0.49	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.078
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1646270344; hg19: chr1-68962639;