Genetic Variant DNAJC21:c.1358+703C>A (chr5-34951045-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012339.3(DNAJC21):c.1358+703C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 985,298 control chromosomes in the GnomAD database, including 332,913 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 41588 hom., cov: 33)

Exomes 𝑓: 0.83 ( 291325 hom. )

Consequence

DNAJC21
NM_001012339.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.917

Publications

9 publications found

Variant links:

Genes affected

DNAJC21 (HGNC:27030): (DnaJ heat shock protein family (Hsp40) member C21) This gene encodes a member of the DNAJ heat shock protein 40 family of proteins that is characterized by two N-terminal tetratricopeptide repeat domains and a C-terminal DNAJ domain. This protein binds the precursor 45S ribosomal RNA and may be involved in early nuclear ribosomal RNA biogenesis and maturation of the 60S ribosomal subunit. Mutations in this gene result in Bone marrow failure syndrome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2017]

DNAJC21 Gene-Disease associations (from GenCC):

bone marrow failure syndrome 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Shwachman-Diamond syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAJC21 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 (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJC21	NM_001012339.3 link	c.1358+703C>A		intron_variant	Intron 10 of 11	ENST00000648817.1	NP_001012339.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJC21	ENST00000648817.1 link	c.1358+703C>A		intron_variant	Intron 10 of 11		NM_001012339.3	ENSP00000497410.1		Q5F1R6-1

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110681

AN:

152026

Hom.:

41567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.547

Gnomad AMI

AF:

0.806

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.834

Gnomad OTH

AF:

0.756

GnomAD4 exome

AF:

0.834

AC:

695126

AN:

833154

Hom.:

291325

Cov.:

AF XY:

0.833

AC XY:

320603

AN XY:

384742

show subpopulations

African (AFR)

AF:

0.517

AC:

8166

AN:

15786

American (AMR)

AF:

0.802

AC:

789

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.769

AC:

3964

AN:

5152

East Asian (EAS)

AF:

0.580

AC:

2106

AN:

3630

South Asian (SAS)

AF:

0.666

AC:

10969

AN:

16462

European-Finnish (FIN)

AF:

0.781

AC:

225

AN:

288

Middle Eastern (MID)

AF:

0.764

AC:

1240

AN:

1622

European-Non Finnish (NFE)

AF:

0.848

AC:

645946

AN:

761928

Other (OTH)

AF:

0.796

AC:

21721

AN:

27302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7543

15085

22628

30170

37713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19740

39480

59220

78960

98700

<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:

0.728

AC:

110735

AN:

152144

Hom.:

41588

Cov.:

AF XY:

0.724

AC XY:

53831

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.547

AC:

22681

AN:

41492

American (AMR)

AF:

0.782

AC:

11953

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2690

AN:

3466

East Asian (EAS)

AF:

0.543

AC:

2801

AN:

5162

South Asian (SAS)

AF:

0.666

AC:

3213

AN:

4822

European-Finnish (FIN)

AF:

0.766

AC:

8118

AN:

10598

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.834

AC:

56735

AN:

68004

Other (OTH)

AF:

0.753

AC:

1591

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1450

2899

4349

5798

7248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.792

Hom.:

142894

Bravo

AF:

0.725

Asia WGS

AF:

0.593

AC:

2065

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.086

(source)

DANN

Benign

0.79

PhyloP100

-0.92

Mutation Taster

=100/0

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