11-73958289-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -2.72

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
DNAJB13	NM_153614.4	c.69-28A>C		intron_variant		ENST00000339764.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB13	ENST00000339764.6	c.69-28A>C		intron_variant		1	NM_153614.4	P1
DNAJB13	ENST00000535730.1	n.113-28A>C		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.419 AC: 104913 AN: 250492 Hom.: 22521 AF XY: 0.420 AC XY: 56953 AN XY: 135460

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 SAS exome AF: 0.495

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

Gnomad4 AFR exome AF: 0.549

Gnomad4 AMR exome AF: 0.351

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.511

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.408

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

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.413

Alfa AF: 0.377 Hom.: 3458

Bravo AF: 0.435

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.042
Dann	Benign	0.23

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

LitVar

Other links and lift over

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