Variant chr20-3190691-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_023935.3(DDRGK1):c.907G>A(p.Ala303Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,878 control chromosomes in the GnomAD database, including 23,621 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1664 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21957 hom. )

Consequence

DDRGK1
NM_023935.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.682

Variant links:

Genes affected

DDRGK1 (HGNC:16110): (DDRGK domain containing 1) The protein encoded by this gene interacts with components of the ubiquitin fold modifier 1 conjugation pathway and helps prevent apoptosis in ER-stressed secretory tissues. In addition, the encoded protein regulates nuclear factor-κB activity. [provided by RefSeq, Dec 2015]

DDRGK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013937354).

BP6

Variant 20-3190691-C-T is Benign according to our data. Variant chr20-3190691-C-T is described in ClinVar as [Benign]. Clinvar id is 1647945.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDRGK1	NM_023935.3 linkuse as main transcript	c.907G>A	p.Ala303Thr	missense_variant	9/9	ENST00000354488.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDRGK1	ENST00000354488.8 linkuse as main transcript	c.907G>A	p.Ala303Thr	missense_variant	9/9	1	NM_023935.3	P1	Q96HY6-1
DDRGK1	ENST00000496781.1 linkuse as main transcript	n.524G>A		non_coding_transcript_exon_variant	2/2	1
DDRGK1	ENST00000470203.1 linkuse as main transcript	n.309G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19362

AN:

152036

Hom.:

1664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.187

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.137

AC:

34330

AN:

250710

Hom.:

2840

AF XY:

0.140

AC XY:

18985

AN XY:

135574

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.0903

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0963

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.166

AC:

242901

AN:

1461724

Hom.:

21957

Cov.:

AF XY:

0.165

AC XY:

120057

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0288

Gnomad4 AMR exome

AF:

0.0948

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0973

Gnomad4 FIN exome

AF:

0.187

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.127

AC:

19356

AN:

152154

Hom.:

1664

Cov.:

AF XY:

0.126

AC XY:

9369

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.120

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0892

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.164

Hom.:

3833

Bravo

AF:

0.116

TwinsUK

AF:

0.183

AC:

680

ALSPAC

AF:

0.176

AC:

678

ESP6500AA

AF:

0.0411

AC:

181

ESP6500EA

AF:

0.184

AC:

1581

ExAC

AF:

0.137

AC:

16569

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.185

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0022

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.74

REVEL

Benign

0.085

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.021

MPC

0.21

ClinPred

0.010

GERP RS

-2.3

Varity_R

0.017

gMVP

0.69

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