Genetic Variant NM_018198.4:c.799G>A (chr1-6645884-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018198.4(DNAJC11):c.799G>A(p.Val267Met) variant causes a missense change. The variant allele was found at a frequency of 0.0787 in 1,614,104 control chromosomes in the GnomAD database, including 5,510 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.064 ( 424 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5086 hom. )

Consequence

DNAJC11
NM_018198.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66

Publications

25 publications found

Variant links:

Genes affected

DNAJC11 (HGNC:25570): (DnaJ heat shock protein family (Hsp40) member C11) Involved in cristae formation. Located in mitochondrial outer membrane and nuclear speck. Part of MIB complex. Colocalizes with MICOS complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021018386).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC11	NM_018198.4 link	c.799G>A	p.Val267Met	missense_variant	Exon 8 of 16	ENST00000377577.10	NP_060668.2	Q9NVH1-1
DNAJC11	XM_047424842.1 link	c.529G>A	p.Val177Met	missense_variant	Exon 6 of 14		XP_047280798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC11	ENST00000377577.10 link	c.799G>A	p.Val267Met	missense_variant	Exon 8 of 16	1	NM_018198.4	ENSP00000366800.5		Q9NVH1-1

Frequencies

GnomAD3 genomes

AF:

0.0636

AC:

9669

AN:

152120

Hom.:

423

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0967

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0483

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0866

Gnomad OTH

AF:

0.0664

GnomAD2 exomes

AF:

0.0732

AC:

18409

AN:

251482

AF XY:

0.0729

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.0632

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.0838

Gnomad OTH exome

AF:

0.0725

GnomAD4 exome

AF:

0.0803

AC:

117327

AN:

1461866

Hom.:

5086

Cov.:

AF XY:

0.0797

AC XY:

57969

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0125

AC:

419

AN:

33480

American (AMR)

AF:

0.115

AC:

5130

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

1757

AN:

26134

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.0524

AC:

4518

AN:

86258

European-Finnish (FIN)

AF:

0.102

AC:

5454

AN:

53418

Middle Eastern (MID)

AF:

0.0388

AC:

224

AN:

5768

European-Non Finnish (NFE)

AF:

0.0861

AC:

95712

AN:

1111994

Other (OTH)

AF:

0.0680

AC:

4104

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5957

11914

17870

23827

29784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3484

6968

10452

13936

17420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0636

AC:

9677

AN:

152238

Hom.:

424

Cov.:

AF XY:

0.0643

AC XY:

4786

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0153

AC:

636

AN:

41550

American (AMR)

AF:

0.0969

AC:

1481

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

209

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5182

South Asian (SAS)

AF:

0.0492

AC:

237

AN:

4820

European-Finnish (FIN)

AF:

0.0993

AC:

1053

AN:

10604

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0866

AC:

5889

AN:

68006

Other (OTH)

AF:

0.0653

AC:

138

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

462

923

1385

1846

2308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0751

Hom.:

1637

Bravo

AF:

0.0590

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0869

AC:

335

ESP6500AA

AF:

0.0170

AC:

ESP6500EA

AF:

0.0823

AC:

708

ExAC

AF:

0.0692

AC:

8406

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0748

EpiControl

AF:

0.0759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.013

.;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

D;D;D;D

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;N;N;.

PhyloP100

5.7

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.28

N;N;N;N

REVEL

Benign

0.093

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.38

T;T;T;.

Polyphen

0.22

B;B;B;.

Vest4

0.097, 0.058

MPC

0.48

ClinPred

0.019

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.053

gMVP

0.21

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over