Variant 8-120001615-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022783.4(DEPTOR):c.695A>G(p.Asn232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,613,924 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

DEPTOR
NM_022783.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0150

Variant links:

Genes affected

DEPTOR (HGNC:22953): (DEP domain containing MTOR interacting protein) Involved in several processes, including negative regulation of TOR signaling; negative regulation of cell size; and negative regulation of protein kinase activity. [provided by Alliance of Genome Resources, Apr 2022]

DEPTOR links:

DEPTOR (HGNC:):

DEPTOR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012125611).

BP6

Variant 8-120001615-A-G is Benign according to our data. Variant chr8-120001615-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2348140.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DEPTOR	NM_022783.4 linkuse as main transcript	c.695A>G	p.Asn232Ser	missense_variant	5/9	ENST00000286234.6	NP_073620.2	Q8TB45-1
DEPTOR	NM_001283012.2 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	3/7		NP_001269941.1	Q8TB45-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DEPTOR	ENST00000286234.6 linkuse as main transcript	c.695A>G	p.Asn232Ser	missense_variant	5/9	1	NM_022783.4	ENSP00000286234.5	Q8TB45-1
DEPTOR	ENST00000523492.5 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	3/7	2		ENSP00000430457.1	Q8TB45-2
DEPTOR	ENST00000518057.1 linkuse as main transcript	n.144A>G		non_coding_transcript_exon_variant	2/6	5

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000402

AC:

101

AN:

251398

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000326

AC:

476

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000400

AC XY:

291

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00146

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.000287

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000289

AC:

AN:

152086

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.3

DANN

Benign

0.74

DEOGEN2

Benign

0.00051

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.17

Sift

Benign

0.52

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0010

.;B

Vest4

0.033

MVP

0.16

MPC

0.12

ClinPred

0.0050

GERP RS

-3.9

Varity_R

0.029

gMVP

0.086

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