rs622064

Variant names:

• chr11-73961529-C-A
• rs622064
• NM_153614.4:c.334+1874C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153614.4(DNAJB13):​c.334+1874C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,974 control chromosomes in the GnomAD database, including 6,998 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 0.29 (6998 hom., cov: 32)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.334+1874C>A		intron_variant	Intron 3 of 7	ENST00000339764.6	NP_705842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB13	ENST00000339764.6	c.334+1874C>A		intron_variant	Intron 3 of 7	1	NM_153614.4	ENSP00000344431.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44551 AN: 151854 Hom.: 6989 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.293 AC: 44587 AN: 151974 Hom.: 6998 Cov.: 32 AF XY: 0.296 AC XY: 22013 AN XY: 74248

African (AFR) AF: 0.388 AC: 16078 AN: 41436

American (AMR) AF: 0.339 AC: 5169 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1149 AN: 5154

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4816

European-Finnish (FIN) AF: 0.356 AC: 3751 AN: 10538

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15591 AN: 67984

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.246 Hom.: 7763

Bravo AF: 0.297

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.087
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: rs622064; hg19: chr11-73672574;