Genetic Variant DNAJB13:c.*41T>C (chr11-73970302-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000543947.1(DNAJB13):c.*41T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 674,744 control chromosomes in the GnomAD database, including 27,554 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 0.28 ( 6208 hom., cov: 32)

Exomes 𝑓: 0.28 ( 21346 hom. )

Consequence

DNAJB13
ENST00000543947.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.635

Publications

18 publications found

Variant links:

Genes affected

DNAJB13 (HGNC:30718): (DnaJ heat shock protein family (Hsp40) member B13) This gene encodes a member of the heat shock protein 40 co-chaperone family which is produced in large amounts in the testis and is located on the radial spokes of the axoneme in human sperm flagella and other flagellar structures. The encoded protein associates with the sperm annulus, as part of the septin complex, through direct interaction with septin 4, during sperm terminal differentiation. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and male infertility. [provided by RefSeq, Apr 2017]

DNAJB13 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 34
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAJB13 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=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4 link	c.*188T>C		downstream_gene_variant		ENST00000339764.6	NP_705842.2	P59910-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAJB13	ENST00000543947.1 link	c.*41T>C	3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000438576.1	P59910-2
DNAJB13	ENST00000339764.6 link	c.*188T>C	downstream_gene_variant		1	NM_153614.4	ENSP00000344431.1	P59910-1
DNAJB13	ENST00000542350.5 link	c.*188T>C	downstream_gene_variant		3		ENSP00000440778.1	H0YFX2
DNAJB13	ENST00000537753.5 link	c.*188T>C	downstream_gene_variant		3		ENSP00000439711.1	P59910-2

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42486

AN:

152008

Hom.:

6211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.281

AC:

146733

AN:

522618

Hom.:

21346

Cov.:

AF XY:

0.277

AC XY:

72706

AN XY:

262270

show subpopulations

African (AFR)

AF:

0.201

AC:

2454

AN:

12216

American (AMR)

AF:

0.342

AC:

3120

AN:

9136

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

3500

AN:

12302

East Asian (EAS)

AF:

0.190

AC:

4675

AN:

24586

South Asian (SAS)

AF:

0.196

AC:

5223

AN:

26668

European-Finnish (FIN)

AF:

0.293

AC:

7380

AN:

25186

Middle Eastern (MID)

AF:

0.324

AC:

653

AN:

2016

European-Non Finnish (NFE)

AF:

0.293

AC:

112380

AN:

383710

Other (OTH)

AF:

0.274

AC:

7348

AN:

26798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4770

9540

14311

19081

23851

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2592

5184

7776

10368

12960

<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:

0.279

AC:

42497

AN:

152126

Hom.:

6208

Cov.:

AF XY:

0.279

AC XY:

20717

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.218

AC:

9064

AN:

41508

American (AMR)

AF:

0.358

AC:

5477

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1022

AN:

3468

East Asian (EAS)

AF:

0.153

AC:

792

AN:

5180

South Asian (SAS)

AF:

0.216

AC:

1041

AN:

4818

European-Finnish (FIN)

AF:

0.310

AC:

3279

AN:

10586

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20733

AN:

67964

Other (OTH)

AF:

0.306

AC:

645

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1601

3202

4804

6405

8006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.291

Hom.:

4598

Bravo

AF:

0.283

Asia WGS

AF:

0.192

AC:

667

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.7

(source)

DANN

Benign

0.49

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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