11-73951088-T-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_153614.4(DNAJB13):c.19T>A(p.Ser7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000535 in 1,614,086 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S7S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (7 hom.)
• Consequence: DNAJB13 NM_153614.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.641

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004512191).
• BP6: Variant 11-73951088-T-A is Benign according to our data. Variant chr11-73951088-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1599261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB13	NM_153614.4	c.19T>A	p.Ser7Thr	missense_variant	1/8	ENST00000339764.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB13	ENST00000339764.6	c.19T>A	p.Ser7Thr	missense_variant	1/8	1	NM_153614.4	P1
DNAJB13	ENST00000535730.1	n.63T>A		non_coding_transcript_exon_variant	1/3	4

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00108 AC: 271 AN: 250360 Hom.: 2 AF XY: 0.00141 AC XY: 191 AN XY: 135432

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00686

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000346

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000558 AC: 815 AN: 1461760 Hom.: 7 Cov.: 30 AF XY: 0.000778 AC XY: 566 AN XY: 727176

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00631

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000182

Gnomad4 OTH exome AF: 0.000480

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74492

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000346 Hom.: 0

Bravo AF: 0.000219

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00111 AC: 135

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	DNAJB13: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -

DNAJB13-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	6.7
Dann	Benign	0.84
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.24	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.15
Sift	Benign	0.045	D
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.15
MVP		0.37
MPC		0.22
ClinPred		0.018	T
GERP RS		-6.0
Varity_R		0.14
gMVP		0.098

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: rs202023755; hg19: chr11-73662133;