Variant 17-17983872-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_031294.4(DRC3):c.205A>G(p.Lys69Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,613,608 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 24 hom. )

Consequence

DRC3
NM_031294.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.82

Variant links:

Genes affected

DRC3 (HGNC:25384): (dynein regulatory complex subunit 3) Located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

DRC3 links:

DRC3 (HGNC:):

DRC3 links:

ATPAF2 (HGNC:18802): (ATP synthase mitochondrial F1 complex assembly factor 2) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 alpha subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. This gene is located within the Smith-Magenis syndrome region on chromosome 17. An alternatively spliced transcript variant has been described, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

ATPAF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01029402).

BP6

Variant 17-17983872-A-G is Benign according to our data. Variant chr17-17983872-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2647535.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRC3	NM_031294.4 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant	4/14	ENST00000399187.6	NP_112584.3	Q9H069-1B3KSC6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DRC3	ENST00000399187.6 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant	4/14	1	NM_031294.4	ENSP00000382140.1	Q9H069-1
DRC3	ENST00000399182.5 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant	4/13	1		ENSP00000382136.1	Q9H069-2
DRC3	ENST00000584166.5 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant	5/14	5		ENSP00000462661.1	Q9H069-2

Frequencies

GnomAD3 genomes

AF:

0.00396

AC:

602

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00544

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00363

AC:

903

AN:

248920

Hom.:

AF XY:

0.00338

AC XY:

457

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00536

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000603

Gnomad NFE exome

AF:

0.00542

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00522

AC:

7622

AN:

1461300

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

3611

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00611

Gnomad4 OTH exome

AF:

0.00552

GnomAD4 genome

AF:

0.00395

AC:

602

AN:

152308

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00544

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00516

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00301

AC:

ESP6500EA

AF:

0.00492

AC:

ExAC

AF:

0.00334

AC:

404

EpiCase

AF:

0.00594

EpiControl

AF:

0.00474

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

Jan 01, 2023

DRC3: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T;.;.;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;D;.;.;D;T;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.010

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.3

D;.;D;.;.;D;.

REVEL

Uncertain

0.32

Sift

Uncertain

0.0050

D;.;D;.;.;D;.

Sift4G

Uncertain

0.051

T;T;T;D;T;D;T

Polyphen

1.0

D;.;D;D;.;D;.

Vest4

0.72

MVP

0.80

MPC

0.84

ClinPred

0.019

GERP RS

5.2

Varity_R

0.60

gMVP

0.75

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