Genetic Variant DEPP1:p.Val9Met (chr10-44978006-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_007021.4(DEPP1):c.25G>A(p.Val9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,458,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

DEPP1
NM_007021.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Publications

0 publications found

Variant links:

Genes affected

DEPP1 (HGNC:23355): (DEPP autophagy regulator 1) The expression of this gene is induced by fasting as well as by progesterone. The protein encoded by this gene contains a t-synaptosome-associated protein receptor (SNARE) coiled-coil homology domain and a peroxisomal targeting signal. Production of the encoded protein leads to phosphorylation and activation of the transcription factor ELK1. [provided by RefSeq, Jul 2008]

DEPP1 links:

RASSF4 (HGNC:20793): (Ras association domain family member 4) The function of this gene has not yet been determined but may involve a role in tumor suppression. Alternative splicing of this gene results in several transcript variants; however, most of the variants have not been fully described. [provided by RefSeq, Jul 2008]

RASSF4 links:

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ACMG classification

Classification was made for transcript

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=0.32478702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007021.4. 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
	DEPP1	NM_007021.4	MANE Select	c.25G>A	p.Val9Met	missense	Exon 2 of 2	NP_008952.1	Q9NTK1
	RASSF4	NM_032023.4	MANE Select	c.139-4515C>T		intron	N/A	NP_114412.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DEPP1	ENST00000298295.4	TSL:1 MANE Select	c.25G>A	p.Val9Met	missense	Exon 2 of 2	ENSP00000298295.3	Q9NTK1
RASSF4	ENST00000340258.10	TSL:1 MANE Select	c.139-4515C>T		intron	N/A	ENSP00000339692.4	Q9H2L5-1
RASSF4	ENST00000489171.5	TSL:1	n.2145-4515C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000367

AC:

AN:

245314

AF XY:

0.0000299

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000895

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1458610

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725688

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.0000683

AC:

AN:

43894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86016

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52312

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111356

Other (OTH)

AF:

0.0000166

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.71

M_CAP

Benign

0.082

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.61

PhyloP100

1.1

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.39

MutPred

0.35

Gain of MoRF binding (P = 0.0767)

MVP

0.71

MPC

0.50

ClinPred

0.88

GERP RS

4.7

Varity_R

0.32

gMVP

0.56

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over