Variant 10-44978006-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32478702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DEPP1	NM_007021.4 linkuse as main transcript	c.25G>A	p.Val9Met	missense_variant	2/2	ENST00000298295.4
RASSF4	NM_032023.4 linkuse as main transcript	c.139-4515C>T		intron_variant		ENST00000340258.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DEPP1	ENST00000298295.4 linkuse as main transcript	c.25G>A	p.Val9Met	missense_variant	2/2	1	NM_007021.4	P1
RASSF4	ENST00000340258.10 linkuse as main transcript	c.139-4515C>T		intron_variant		1	NM_032023.4	P1	Q9H2L5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000367

AC:

AN:

245314

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133938

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 SAS exome

AF:

0.0000987

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000683

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.25G>A (p.V9M) alteration is located in exon 2 (coding exon 1) of the C10orf10 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the valine (V) at amino acid position 9 to be replaced by a methionine (M). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.13

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.082

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

D;D;D;N

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.39

MutPred

0.35

Gain of MoRF binding (P = 0.0767);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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over