7-73683324-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_032317.3(DNAJC30):c.100G>A(p.Gly34Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,613,630 control chromosomes in the GnomAD database, including 143,552 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10687 hom., cov: 34)

Exomes 𝑓: 0.42 ( 132865 hom. )

Consequence

DNAJC30
NM_032317.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.486

Publications

42 publications found

Variant links:

Genes affected

DNAJC30 (HGNC:16410): (DnaJ heat shock protein family (Hsp40) member C30) This intronless gene encodes a member of the DNAJ molecular chaperone homology domain-containing protein family. This gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.23. [provided by RefSeq, Jul 2008]

DNAJC30 Gene-Disease associations (from GenCC):

Leber hereditary optic neuropathy, autosomal recessive
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Leber hereditary optic neuropathy
Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

DNAJC30 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: -1.0791 (below the threshold of 3.09). Trascript score misZ: -0.20689 (below the threshold of 3.09). GenCC associations: The gene is linked to Leber hereditary optic neuropathy, Leber hereditary optic neuropathy, autosomal recessive.

BP4

Computational evidence support a benign effect (MetaRNN=4.937053E-4).

BP6

Variant 7-73683324-C-T is Benign according to our data. Variant chr7-73683324-C-T is described in ClinVar as Benign. ClinVar VariationId is 1254123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC30	NM_032317.3 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 1 of 1	ENST00000395176.3	NP_115693.2	Q96LL9B3KSU4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC30	ENST00000395176.3 link	c.100G>A	p.Gly34Arg	missense_variant	Exon 1 of 1	6	NM_032317.3	ENSP00000378605.1		Q96LL9

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54664

AN:

152126

Hom.:

10688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.441

Gnomad EAS

AF:

0.353

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.390

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.382

GnomAD2 exomes

AF:

0.383

AC:

94745

AN:

247294

AF XY:

0.389

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.269

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.401

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.422

AC:

616823

AN:

1461386

Hom.:

132865

Cov.:

102

AF XY:

0.421

AC XY:

305935

AN XY:

726980

show subpopulations

African (AFR)

AF:

0.211

AC:

7061

AN:

33480

American (AMR)

AF:

0.279

AC:

12500

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

11305

AN:

26136

East Asian (EAS)

AF:

0.309

AC:

12251

AN:

39700

South Asian (SAS)

AF:

0.342

AC:

29476

AN:

86258

European-Finnish (FIN)

AF:

0.399

AC:

21121

AN:

52926

Middle Eastern (MID)

AF:

0.521

AC:

3003

AN:

5766

European-Non Finnish (NFE)

AF:

0.445

AC:

495297

AN:

1112000

Other (OTH)

AF:

0.411

AC:

24809

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

27141

54282

81422

108563

135704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14698

29396

44094

58792

73490

<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:

0.359

AC:

54675

AN:

152244

Hom.:

10687

Cov.:

AF XY:

0.356

AC XY:

26505

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.213

AC:

8865

AN:

41562

American (AMR)

AF:

0.321

AC:

4913

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.441

AC:

1528

AN:

3468

East Asian (EAS)

AF:

0.353

AC:

1823

AN:

5164

South Asian (SAS)

AF:

0.332

AC:

1606

AN:

4832

European-Finnish (FIN)

AF:

0.390

AC:

4126

AN:

10590

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.448

AC:

30469

AN:

68004

Other (OTH)

AF:

0.379

AC:

802

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1856

3713

5569

7426

9282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.415

Hom.:

56131

Bravo

AF:

0.348

TwinsUK

AF:

0.460

AC:

1706

ALSPAC

AF:

0.455

AC:

1755

ESP6500AA

AF:

0.211

AC:

923

ESP6500EA

AF:

0.448

AC:

3837

ExAC

AF:

0.383

AC:

46416

Asia WGS

AF:

0.298

AC:

1038

AN:

3478

EpiCase

AF:

0.452

EpiControl

AF:

0.449

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 07, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

5.7

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.40

MetaRNN

Benign

0.00049

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.95

PhyloP100

-0.49

PrimateAI

Benign

0.36

PROVEAN

Benign

0.050

REVEL

Benign

0.059

Sift

Benign

0.61

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.022

MutPred

0.14

Gain of sheet (P = 0.0507);

MPC

0.47

ClinPred

0.0011

GERP RS

-1.8

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.044

gMVP

0.20

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over