11-73958265-C-A

Variant names:

• chr11-73958265-C-A
• rs10793068
• NM_153614.4:c.69-52C>A

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.69-52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,580,670 control chromosomes in the GnomAD database, including 133,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17609 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115769 hom.)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.20
• Publications: 19 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=-0.91).
• BP6: Variant 11-73958265-C-A is Benign according to our data. Variant chr11-73958265-C-A is described in ClinVar as [Benign]. Clinvar id is 1259292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.69-52C>A		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.69-52C>A		intron_variant	Intron 1 of 7	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.113-52C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70909 AN: 151860 Hom.: 17578 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.445

GnomAD4 exome AF: 0.399 AC: 569519 AN: 1428692 Hom.: 115769 Cov.: 25 AF XY: 0.401 AC XY: 285493 AN XY: 712674

African (AFR) AF: 0.654 AC: 21508 AN: 32874

American (AMR) AF: 0.356 AC: 15847 AN: 44494

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9800 AN: 25838

East Asian (EAS) AF: 0.510 AC: 20165 AN: 39514

South Asian (SAS) AF: 0.466 AC: 39849 AN: 85562

European-Finnish (FIN) AF: 0.471 AC: 24523 AN: 52084

Middle Eastern (MID) AF: 0.397 AC: 2259 AN: 5696

European-Non Finnish (NFE) AF: 0.379 AC: 411120 AN: 1083364

Other (OTH) AF: 0.413 AC: 24448 AN: 59266

GnomAD4 genome AF: 0.467 AC: 70991 AN: 151978 Hom.: 17609 Cov.: 32 AF XY: 0.469 AC XY: 34817 AN XY: 74262

African (AFR) AF: 0.642 AC: 26639 AN: 41462

American (AMR) AF: 0.389 AC: 5934 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1296 AN: 3464

East Asian (EAS) AF: 0.477 AC: 2454 AN: 5146

South Asian (SAS) AF: 0.463 AC: 2231 AN: 4820

European-Finnish (FIN) AF: 0.472 AC: 4983 AN: 10568

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26173 AN: 67948

Other (OTH) AF: 0.444 AC: 935 AN: 2108

Alfa AF: 0.404 Hom.: 38538

Bravo AF: 0.467

Asia WGS AF: 0.500 AC: 1738 AN: 3478

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	-0.91
CADD	Benign	0.37
DANN	Benign	0.71
PhyloP100		-1.2
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: rs10793068; hg19: chr11-73669310; COSMIC: COSV60269602;