Genetic Variant DNAJB13:c.721-228G>A (chr11-73969018-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_153614.4(DNAJB13):c.721-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,930 control chromosomes in the GnomAD database, including 25,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 25555 hom., cov: 32)

Consequence

DNAJB13
NM_153614.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.179

Publications

8 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAJB13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-73969018-G-A is Benign according to our data. Variant chr11-73969018-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231202.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153614.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DNAJB13	NM_153614.4	MANE Select	c.721-228G>A	intron	N/A	NP_705842.2
DNAJB13	NM_001441321.1		c.559-228G>A	intron	N/A	NP_001428250.1
DNAJB13	NM_001377263.1		c.547-228G>A	intron	N/A	NP_001364192.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJB13	ENST00000339764.6	TSL:1 MANE Select	c.721-228G>A	intron	N/A	ENSP00000344431.1	P59910-1
DNAJB13	ENST00000543947.1	TSL:1	c.196-228G>A	intron	N/A	ENSP00000438576.1	P59910-2
DNAJB13	ENST00000897971.1		c.559-228G>A	intron	N/A	ENSP00000568030.1

Frequencies

GnomAD3 genomes

AF:

0.558

AC:

84695

AN:

151812

Hom.:

25535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.814

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.452

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.558

AC:

84760

AN:

151930

Hom.:

25555

Cov.:

AF XY:

0.555

AC XY:

41180

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.814

AC:

33732

AN:

41462

American (AMR)

AF:

0.525

AC:

8013

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.445

AC:

1542

AN:

3462

East Asian (EAS)

AF:

0.429

AC:

2221

AN:

5176

South Asian (SAS)

AF:

0.399

AC:

1918

AN:

4812

European-Finnish (FIN)

AF:

0.495

AC:

5212

AN:

10526

Middle Eastern (MID)

AF:

0.445

AC:

129

AN:

290

European-Non Finnish (NFE)

AF:

0.449

AC:

30516

AN:

67916

Other (OTH)

AF:

0.530

AC:

1118

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.513

Hom.:

4564

Bravo

AF:

0.573

Asia WGS

AF:

0.437

AC:

1517

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.12

(source)

DANN

Benign

0.49

PhyloP100

-0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over