11-73958265-C-A

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.69-52C>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, single submitter B:1
• Conservation: PhyloP100: -1.20

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=-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_single_submitter, 1 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/exons	MANE	UniProt
DNAJB13	NM_153614.4	c.69-52C>A		intron_variant		ENST00000339764.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB13	ENST00000339764.6	c.69-52C>A		intron_variant		1	NM_153614.4	P1
DNAJB13	ENST00000535730.1	n.113-52C>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR exome AF: 0.654

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.510

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.413

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

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.444

Alfa AF: 0.382 Hom.: 14750

Bravo AF: 0.467

Asia WGS AF: 0.500 AC: 1738 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.37
Dann	Benign	0.71

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: rs10793068; hg19: chr11-73669310; COSMIC: COSV60269602;