1-68477878-G-A

Variant names:

• chr1-68477878-G-A
• rs374648098
• NM_001114120.3:c.2207C>T

Variant summary

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

The NM_001114120.3(DEPDC1):​c.2207C>T​(p.Ser736Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,437,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S736C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DEPDC1 NM_001114120.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.07
• Publications: 0 publications found

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]

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=0.28270668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114120.3. 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
	DEPDC1	NM_001114120.3	MANE Select	c.2207C>T	p.Ser736Phe	missense	Exon 11 of 12	NP_001107592.1	Q5TB30-5
	DEPDC1	NM_017779.6		c.1355C>T	p.Ser452Phe	missense	Exon 10 of 11	NP_060249.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DEPDC1	ENST00000456315.7	TSL:1 MANE Select	c.2207C>T	p.Ser736Phe	missense	Exon 11 of 12	ENSP00000412292.2	Q5TB30-5
	DEPDC1	ENST00000370966.9	TSL:1	c.1355C>T	p.Ser452Phe	missense	Exon 10 of 11	ENSP00000360005.5	Q5TB30-2
	DEPDC1	ENST00000489862.1	TSL:1	n.*424C>T		non_coding_transcript_exon	Exon 12 of 13	ENSP00000436464.1	H0YES2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437666 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 713824

African (AFR) AF: 0.00 AC: 0 AN: 32942

American (AMR) AF: 0.00 AC: 0 AN: 42928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39116

South Asian (SAS) AF: 0.00 AC: 0 AN: 79652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 9.10e-7 AC: 1 AN: 1099444

Other (OTH) AF: 0.00 AC: 0 AN: 59352

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.1
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Uncertain	0.036	D
Polyphen		0.88	P
Vest4		0.45
MutPred		0.32		Loss of disorder (P = 0.0132)
MVP		0.59
MPC		0.56
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.23
gMVP		0.41
Mutation Taster		=77/23	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: rs374648098; hg19: chr1-68943561;