rs2306819

chr11-73970045-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_153614.4(DNAJB13):c.882C>T(p.Phe294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,609,274 control chromosomes in the GnomAD database, including 68,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6202 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62442 hom.)
• Consequence: DNAJB13 NM_153614.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 11-73970045-C-T is Benign according to our data. Variant chr11-73970045-C-T is described in ClinVar as [Benign]. Clinvar id is 1253105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB13	NM_153614.4	c.882C>T	p.Phe294=	synonymous_variant	8/8	ENST00000339764.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB13	ENST00000339764.6	c.882C>T	p.Phe294=	synonymous_variant	8/8	1	NM_153614.4	P1
DNAJB13	ENST00000543947.1	c.357C>T	p.Phe119=	synonymous_variant	5/6	1
DNAJB13	ENST00000542350.5	c.585C>T	p.Phe195=	synonymous_variant	5/5	3
DNAJB13	ENST00000537753.5	c.357C>T	p.Phe119=	synonymous_variant	5/5	3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42433 AN: 151876 Hom.: 6205 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.309

GnomAD3 exomes AF: 0.285 AC: 69953 AN: 245486 Hom.: 10677 AF XY: 0.282 AC XY: 37434 AN XY: 132906

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.290 AC: 422136 AN: 1457280 Hom.: 62442 Cov.: 35 AF XY: 0.288 AC XY: 208524 AN XY: 724702

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.279 AC: 42443 AN: 151994 Hom.: 6202 Cov.: 32 AF XY: 0.279 AC XY: 20689 AN XY: 74278

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.305

Alfa AF: 0.302 Hom.: 8716

Bravo AF: 0.283

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	4.3
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2306819; hg19: chr11-73681090; COSMIC: COSV60104595; COSMIC: COSV60104595;