11-73958289-A-C

Variant names:

• chr11-73958289-A-C
• rs10793069
• NM_153614.4:c.69-28A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153614.4(DNAJB13):​c.69-28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,609,168 control chromosomes in the GnomAD database, including 132,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15149 hom., cov: 32)
  • Exomes 𝑓: 0.40 (117764 hom.)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.72
• Publications: 15 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 11-73958289-A-C is Benign according to our data. Variant chr11-73958289-A-C is described in ClinVar as [Benign]. Clinvar id is 1271046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.69-28A>C		intron_variant	Intron 1 of 7	ENST00000339764.6	NP_705842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB13	ENST00000339764.6	c.69-28A>C		intron_variant	Intron 1 of 7	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.113-28A>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66836 AN: 151934 Hom.: 15124 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.419 AC: 104913 AN: 250492 AF XY: 0.420

Gnomad AFR exome AF: 0.540

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.471

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.399 AC: 580697 AN: 1457116 Hom.: 117764 Cov.: 30 AF XY: 0.402 AC XY: 291382 AN XY: 725262

African (AFR) AF: 0.549 AC: 18305 AN: 33368

American (AMR) AF: 0.351 AC: 15667 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9916 AN: 26104

East Asian (EAS) AF: 0.511 AC: 20253 AN: 39658

South Asian (SAS) AF: 0.493 AC: 42453 AN: 86150

European-Finnish (FIN) AF: 0.474 AC: 25150 AN: 53066

Middle Eastern (MID) AF: 0.387 AC: 2234 AN: 5766

European-Non Finnish (NFE) AF: 0.381 AC: 422163 AN: 1108108

Other (OTH) AF: 0.408 AC: 24556 AN: 60224

GnomAD4 genome AF: 0.440 AC: 66907 AN: 152052 Hom.: 15149 Cov.: 32 AF XY: 0.444 AC XY: 32960 AN XY: 74294

African (AFR) AF: 0.539 AC: 22346 AN: 41494

American (AMR) AF: 0.376 AC: 5739 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1306 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2457 AN: 5140

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4818

European-Finnish (FIN) AF: 0.473 AC: 5003 AN: 10574

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26444 AN: 67974

Other (OTH) AF: 0.413 AC: 869 AN: 2106

Alfa AF: 0.387 Hom.: 4060

Bravo AF: 0.435

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.042
DANN	Benign	0.23
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10793069; hg19: chr11-73669334; COSMIC: COSV60269608;