Variant 6-83129133-G-A 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_015018.4(DOP1A):c.1966G>A(p.Val656Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,613,750 control chromosomes in the GnomAD database, including 7 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 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

DOP1A
NM_015018.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

Variant links:

Genes affected

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

DOP1A 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=0.0033484697).

BP6

Variant 6-83129133-G-A is Benign according to our data. Variant chr6-83129133-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656726.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1A	NM_015018.4 linkuse as main transcript	c.1966G>A	p.Val656Ile	missense_variant	16/39	ENST00000349129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DOP1A	ENST00000349129.7 linkuse as main transcript	c.1966G>A	p.Val656Ile	missense_variant	16/39	1	NM_015018.4	P4
DOP1A	ENST00000369739.7 linkuse as main transcript	c.1939G>A	p.Val647Ile	missense_variant	15/39	1		A1
DOP1A	ENST00000237163.9 linkuse as main transcript	c.1939G>A	p.Val647Ile	missense_variant	16/40	5		A1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00178

AC:

445

AN:

250034

Hom.:

AF XY:

0.00181

AC XY:

244

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.000699

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000918

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00212

AC:

3097

AN:

1461482

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1551

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.000460

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000847

Gnomad4 FIN exome

AF:

0.00172

Gnomad4 NFE exome

AF:

0.00248

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152268

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00198

AC:

241

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

DOP1A: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.0020

DANN

Benign

0.60

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.69

T;T;.

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

REVEL

Benign

0.026

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.044

MVP

0.043

MPC

0.21

ClinPred

0.0033

GERP RS

-11

Varity_R

0.022

gMVP

0.10

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